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  • 101.
    Fischerström, Ann
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nyholm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Acute neurosurgery for traumatic brain injury by general surgeons in Swedish county hospitals: A regional study2014Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 156, nr 1, s. 177-185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traditionally acute life-saving evacuations of extracerebral haematomas are performed by general surgeons on vital indication in county hospitals in the Uppsala-A-rebro health care region in Sweden, a region characterized by long distances and a sparsely distributed population. Recently, it was stated in the guidelines for prehospital care of traumatic brain injury from the Scandinavian Neurosurgical Society that acute neurosurgery should not be performed in smaller hospitals without neurosurgical expertise. The aim of this study was to investigate: how often does acute decompressive neurosurgery occur in county hospitals in the Uppsala-A-rebro region today, what is the indication for surgery, and what is the clinical outcome? Finally, the goal was to evaluate whether the current practice in the Uppsala-A-rebro region should be revised. Patients referred to the neurointensive care unit at the Department of Neurosurgery in Uppsala after acute evacuation of intracranial haematomas in the county hospitals 2005-2010 were included in the study. Data was collected retrospectively from the medical records following a predefined protocol. The presence of vital indication, radiological and clinical results, and long-term outcome were evaluated. A total of 49 patients (17 epidural haematomas and 32 acute subdural haematomas) were included in the study. The operation was judged to have been performed on vital indication in all cases. The postoperative CT scan was improved in 92 % of the patients. The reaction level and pupillary reactions were significantly improved after surgery. Long-term outcomes showed 51 % favourable outcome, 33 % unfavourable outcome, and in 16 % the outcome was unknown. Looking at the indication for acute neurosurgery, the postoperative clinical and radiological results, and the long-term outcome, it appears that our regional policy regarding life-saving decompressive neurosurgery in county hospitals by general surgeons should not be changed. We suggest a curriculum aimed at educating general surgeons in acute neurosurgery.

  • 102. Fisher, James L.
    et al.
    Pettersson, David
    Palmisano, Sadie
    Schwartzbaum, Judith A.
    Edwards, Colin G.
    Mathiesen, Tiit
    Prochazka, Michaela
    Bergenheim, Tommy
    Florentzson, Rut
    Harder, Henrik
    Nyberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Siesjo, Peter
    Feychting, Maria
    Loud Noise Exposure and Acoustic Neuroma2014Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, nr 1, s. 58-67Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.

  • 103.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts2016Konferansepaper (Fagfellevurdert)
  • 104.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts2017Inngår i: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627, Vol. 35, nr 2, s. 251-263Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.

    Objective: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.

    Methods: Proliferation of OPCs was evaluated in 27 cFPI mice using 5-ethynyl-2-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n=9), 7 (n = 8) and 21 (n = 10) days post injury (dpi). Sham-injured mice (n = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle.

    Results: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 days post-injury (dpi; p≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae.

    Conclusion: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies.

  • 105.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Djupsjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lenne, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat2013Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 38, nr 1, s. 2153-2165Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ≤ 0.05). Accumulation of β-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ≤ 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.

  • 106.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gumucio, Astrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Uppsala, Sweden..
    Skoglund, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Holm, Jonatan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells2016Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 75, nr 6, s. 503-515Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 +/- 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 +/- 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-alpha were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-alpha-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI.

  • 107.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ruscher, Karsten
    Department of Neuroscience, unit of Neurosurgery, Lund University, Lund, Sweden..
    Norberg, Amanda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mir, AK
    Novartis Institutes of Biomedical Research, Basel, Switzerland .
    Gram, Hermann
    Novartis Institutes of Biomedical Research, Basel, Switzerland .
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Reduced loss of mature Oligodendrocytes following Diffuse Traumatic Brain Injury in the mouse by Neutralization of Interleukin-1βManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Abstract

    Background: Traumatic brain injury (TBI) leads to several secondary consequences impairing patient outcome. Injury to the components of the white matter, the oligodendrocyte population, myelin and axons, associate with post-injury cognitive deficits. Oligodendrocytes (OLs), the myelin-producing cell, are highly vulnerable post-TBI. Lost OLs may be replaced by proliferating oligodendrocyte progenitor cells (OPCs). A complex inflammatory response is also initiated following TBI, which is an important therapeutic target in TBI. The cytokine, interleukin-1β (IL-1β), is a key mediator of the inflammatory response. When neutralized following experimental TBI, behavioral and histological outcome is improved by unknown mechanisms.

    Methods: The central fluid percussion injury (cFPI) and sham injury was used in mice at three survival end-points; 2, 7 and 14 days post-injury. Mice were, at 30 min post-injury, randomly administered a neutralizing IL-1β antibody or a control antibody.  OPC proliferation (5-ethynyl 2´- deoxyuridine (EdU)/Olig 2 co-labeling) and mature OL cell death was evaluated in injured white matter tracts. In situ hybridization for Olig2 transcripts in EdU positive cells and microglia ramification was also evaluated.

    Results: Attenuated cell death, indicated by cleaved caspase-3 expression, and OL cell loss was observed in brain-injured animals treated with the IL-1β neutralizing antibody without influencing proliferation of OPCs, the number of Olig2 transcript or the ramification of microglia. 

     

    Conclusion: Although OPC proliferation was not influenced, IL-1β neutralization reduced oligodendrocyte cell death in diffuse TBI which may partly explain the beneficial outcome observed using this anti-inflammatory treatment.   

     

  • 108.
    Flygt, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ruscher, Karsten
    Novartis Inst Biomed Res, Basel, Switzerland.
    Norberg, Amanda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Mir, Anis
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Gram, Hermann
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Neutralization of Interleukin-1 beta following Diffuse Traumatic Brain Injury in the Mouse Attenuates the Loss of Mature Oligodendrocytes2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 23, s. 2837-2849Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1 beta (IL-1 beta) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1 beta on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min post-injury, mice were randomly administered an IL-1 beta neutralizing or a control antibody. OPC proliferation (5-ethynyl 2 '- deoxyuridine (EdU)/Olig2 co-labeling) and mature oligodendrocyte cell loss was evaluated in injured white matter tracts. Microglia/macrophages immunohistochemistry and ramification using Sholl analysis were also evaluated. Neutralizing IL-1 beta resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and attenuated loss of mature OLs from two to seven days post-injury in brain-injured animals. IL-1 beta neutralization also attenuated the early, two day post-injury increase of microglia/macrophage immunoreactivity and altered their ramification. The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1 beta is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1 beta neutralization in this mouse model of diffuse TBI.

  • 109. Freyschlag, Christian F
    et al.
    Krieg, Sandro M
    Kerschbaumer, Johannes
    Pinggera, Daniel
    Forster, Marie-Therese
    Cordier, Dominik
    Rossi, Marco
    Miceli, Gabriele
    Roux, Alexandre
    Reyes, Andrés
    Sarubbo, Silvio
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Sierpowska, Joanna
    Robe, Pierre A
    Rutten, Geert-Jan
    Santarius, Thomas
    Matys, Tomasz
    Zanello, Marc
    Almairac, Fabien
    Mondot, Lydiane
    Jakola, Asgeir S
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Rofes, Adrià
    von Campe, Gord
    Guillevin, Remy
    Bagatto, Daniele
    Lubrano, Vincent
    Rapp, Marion
    Goodden, John
    De Witt Hamer, Philip C
    Pallud, Johan
    Bello, Lorenzo
    Thomé, Claudius
    Duffau, Hugues
    Mandonnet, Emmanuel
    Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.2018Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 139, nr 3, s. 699-711Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.

    METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.

    RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.

    CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.

    IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

  • 110.
    Fridgeirsdottir, Gudrun Andrea
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Escalated handling of young C57BL/6 mice results in altered Morris water maze performance2014Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, nr 1, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. The handling of experimental animals prior to experimental interventions is often poorly described, even though it may affect the final functional outcome. This study explores how the use of repeated handling of C57BL/6 mice prior to Morris water maze (MWM) tests can affect the performance. Methods and materials. The handled animals were subjected to the escalating handling protocol, with the investigator spending 5 min per day per cage for 8 days prior to the MWM test. On the last days of handling, the mice were introduced to water and the concept of a hidden platform. The MWM test consisted of four daily trials for 90 s per day for 4 days with a hidden platform. A probe test was performed 4 days after the last learning trial. Control animals were not handled prior to MWM. Results. Handling reduced the latency to find the platform on the first 2 days of the MWM tests and reduced thigmotaxis. The mice increased their swim speed and elicited more explorative behavior in the learning trials and to some lesser extent in the probe trials. Conclusions. The improvement in MWM navigation was most likely due to reduced stress and anxiety regarding the investigator and the test. Handled mice displayed less variability than non-handled mice, suggesting that by using a controlled handling protocol prior to the experiments fewer C57BL/6 mice would be needed to achieve statistically significant differences in studies of learning and spatial memory using MWM.

  • 111.
    Frykholm, Peter
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cerebral ischemia studied with positron emission tomography and microdialysis2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Stroke is the third leading cause of morbidity and mortality in the industrialized world. Subarachnoid hemorrhage (SAH), the least common form of stroke, is one of the most demanding diseases treated in neurointensive care units. Cerebral ischemia may develop rapidly, and has a major influence on outcome.To be able to save parts of the brain that are at risk for ischemic brain damage, there is a need for reliable monitoring techniques. Understanding the pathophysiology of cerebral ischemia is a prerequisite both for the correct treatment of these diseases and for the development of new monitoring techniques and treatment modalities. The main aim of this thesis was to gain insight into the mechanisms of cerebral ischemia by studying early hemodynamic and metabolic changes with positron emission tomography and neurochemical changes with microdialysis. A secondary aim was to evaluate the potential of these techniques for detecting ischemia and predicting the degree of reversibility of ischemic changes.

    Early changes in cerebral blood flow (CBF) and metabolism (CMRO2) were studied with repeated positron emission tomography in an experimental model (MCAO) of transient focal ischemia, and in SAH patients. CMRO2 was superior to CBF in discriminating between tissue with irreversible damage and tissue with the potential for survival in the experimental model. A metabolic threshold of ischemia was found. Neurochemical changes in the ischemic regions were studied simultaneously with microdialysis. Extracellular concentrations of glucose, lactate, hypoxanthine, glutamate and glycerol were measured, and the lactate/pyruvate (LP) and lactate/glucose ratios were calculated. Changes in all the microdialysis parameters were related to the degree of ischemia (severe ischemia or penumbra). Especially the LP ratio and glycerol were found to be robust and specific markers of ischemia. In the patients, hemodynamic and metabolic changes were common, but diverse in the acute phase of SAH, and it was suggested that these changes may contribute to an increased vulnerability for secondary events and the development of secondary ischemic brain damage.

  • 112.
    Fytagoridis, A.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden.;Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Jiltsova, E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Heard, T.
    Univ Queensland, Asia Pacific Ctr Neuromodulat, Brisbane, Qld, Australia..
    Samuelsson, J.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Zsigmond, P.
    Linkoping Univ Hosp, Dept Neurosurg, Linkoping, Sweden..
    Skyrman, S.
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden..
    Surgical replacement of Implantable pulse generators in deep brain stimulation: adverse events and risk factors in a multicenter cohort2016Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 123, nr 12, s. 1512-1512Artikkel i tidsskrift (Annet vitenskapelig)
  • 113.
    Fytagoridis, Anders
    et al.
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden.;Umeå Univ, Dept Pharmacol & Clin Neurosci, Unit Funct & Stereotact Neurosurg, Umeå, Sweden.;Univ Queensland, Queensland Brain Inst, Asia Pacific Ctr Neuromodulat, Brisbane, Qld 4072, Australia..
    Heard, Tomas
    Univ Queensland, Queensland Brain Inst, Asia Pacific Ctr Neuromodulat, Brisbane, Qld 4072, Australia..
    Samuelsson, Jennifer
    Umeå Univ, Dept Pharmacol & Clin Neurosci, Unit Funct & Stereotact Neurosurg, Umeå, Sweden.;Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden..
    Zsigmond, Peter
    Linköping Univ Hosp, Dept Neurosurg, Linköping, Sweden..
    Jiltsova, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Skyrman, Simon
    Karolinska Inst, Dept Clin Neurosci, Neurosurg, Stockholm, Sweden..
    Skoglund, Thomas
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden..
    Coyne, Terry
    Univ Queensland, Queensland Brain Inst, Asia Pacific Ctr Neuromodulat, Brisbane, Qld 4072, Australia.;Brizbrain & Spine, Brisbane, Qld, Australia..
    Silburn, Peter
    Univ Queensland, Queensland Brain Inst, Asia Pacific Ctr Neuromodulat, Brisbane, Qld 4072, Australia..
    Blomstedt, Patric
    Umeå Univ, Dept Pharmacol & Clin Neurosci, Unit Funct & Stereotact Neurosurg, Umeå, Sweden..
    Surgical Replacement of Implantable Pulse Generator in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort2016Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, nr 4, s. 235-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements.

  • 114.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Silander, H C
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation2000Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, nr 5, s. 1423-1430Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.

    DESIGN:

    Randomized controlled study.

    SETTING:

    University hospital research laboratory.

    SUBJECTS:

    A total of 20 male anesthetized piglets.

    INTERVENTIONS:

    Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.

    MEASUREMENTS AND MAIN RESULTS:

    Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.

    CONCLUSIONS:

    Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.

  • 115.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Umeå.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Beskow, Anna H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Birgisson, Helgi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Björ, Ove
    Umeå Univ, Dept Radiat Sci, Umeå.
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hansson, Tony
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Henriksson, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Jonsson, Håkan
    Umeå Univ, Dept Radiat Sci, Umeå.
    Larsson, Chatarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ljuslinder, Ingrid
    Umeå Univ, Dept Radiat Sci, Umeå.
    Mindus, Stephanie
    Akad Sjukhuset, Lung & Allergy Clin, Uppsala.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sandin, Fredrik
    Uppsala Univ Hosp, RCC Uppsala Örebro, Uppsala.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Solna.
    Stenling, Roger
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sundström, Christer Sundström
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Thellenberg Karlsson, Camilla
    Umeå Univ, Dept Radiat Sci, Umeå.
    Westermark, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Bergh, Anders
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Claesson-Welsh, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Palmqvist, Richard
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Sjöblom, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 187-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 116.
    Gunther, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Danckwardt-Lillieström, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nyberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kinnefors, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ekvall, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Surgical Treatment of Patients With Facial Neuromas: A Report of 26 Consecutive Operations2010Inngår i: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 31, nr 9, s. 1493-1497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To analyze surgical treatment and outcome in patients with facial neuromas at a tertiary referral hospital. Study Design: A chart review of 26 patients treated between 1971 and 2006, with questionnaire follow-up ranging from 2 to 19 years. All patients except one were operated with radical tumor removal approaches. Results: Approximately 54% of the patients presented with symptoms related to the VIIth cranial nerve (facial palsy and facial spasm), 58% with symptoms related to the VIIIth cranial nerve (hearing deficit, tinnitus, and vertigo), and 8% related to the Vth cranial nerve (facial pain and facial sensory deficit). Approximately 39% presented with no facial symptoms. Twenty-one patients received a facial nerve graft from the greater auricular nerve or the sural nerve; 1 patient had an accessory-facial anastomosis. One patient had a subtotal tumor removal preserving the facial nerve. Three patients were not grafted. Most tumors (88%) affect the geniculate ganglion. Approximately 82% of the grafted patients regained a House-Brackmann facial nerve function (HB) grade III; 14% regained HB grades IV to V. No serious morbidity or mortality was reported. No recurrences have been reported where a total tumor removal was performed. Conclusion: Surgical removal of facial neuroma is a safe procedure with a low complication rate and a low recurrence rate. First symptoms are diverse and are predominantly derived from the facial and vestibulocochlear nerve. Facial nerve grafting is reliable, giving the patient an acceptable facial nerve function (HB III).

  • 117.
    Hagberg, Hans
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Blomkvist, E
    Pontén, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Persson, C
    Muhr, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Olsson, Y
    Lilja, A
    Does alpha-interferon in conjunctions with radiotheraphy increase the risk of complications in the central nervous system?1990Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 1, nr 6, s. 449-451Artikkel i tidsskrift (Fagfellevurdert)
  • 118. Hagerstrand, Daniel
    et al.
    He, Xiaobing
    Lindh, Maja Bradic
    Hoefs, Saskia
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ostman, Arne
    Nister, Monica
    Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile2011Inngår i: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 13, nr 11, s. 1178-1191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemoresistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies. Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets, designated type A and type B cultures. The type A cultures displayed high expression of CXCR4, SOX2, EAAT1, and GFAP and low expression of CNP, PDGFRB, CXCL12, and extracellular matrix proteins. Clinical significance of the 2 types was indicated by the expression of type A-and type B-defining genes in different clinical glioblastoma samples. Classification of glioblastomas with type A- and type B-defining genes generated 2 groups of tumors composed predominantly of the classical, neural, and/or proneural subsets and the mesenchymal subset, respectively. Furthermore, tumors with EGFR mutations were enriched in the group of type A samples. Type A cultures possessed a higher capacity to form xenograft tumors and neurospheres and displayed low or no sensitivity to monotreatment with PDGF-and IGF-1-receptor inhibitors but were efficiently growth inhibited by combination treatment with low doses of these 2 inhibitors. Furthermore, siRNA-induced downregulation of SOX2 reduced sphere formation of type A cultures, decreased expression of type A-defining genes, and conferred sensitivity to monotreatment with PDGF-and IGF-1receptor inhibitors. The present study thus describes a tumor-and neurosphere-forming SOX2-dependent subset of glioblastoma cultures characterized by a gene expression signature similar to that of the recently described classical, proneural, and/or neural subsets of glioblastoma. The findings that resistance to PDGF-and IGF-1-receptor inhibitors is related to SOX2 expression and can be overcome by combination treatment should be considered in ongoing efforts to develop novel stem cell-targeting therapies.

  • 119.
    Halawa, Imad
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Vlachogiannis, Pavlos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Amandusson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Elf, Kristin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Zetterberg, H.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage2018Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, nr 2, s. 199-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI.

    Methods

    We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T-tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome.

    Results

    Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055-1.680. P=.016].

    Conclusion

    Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI.

  • 120.
    Hanell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Djupsjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Vallstedt, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Patra, Kalicharan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Israelsson, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Larhammar, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Björk, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Paixao, Sonia
    Kullander, Klas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Functional and Histological Outcome after Focal Traumatic Brain Injury Is Not Improved in Conditional EphA4 Knockout Mice2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 17, s. 2660-2671Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p < 0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p < 0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p < 0.05) and hippocampal sprouting (Timm stain, p < 0.05) and induced a marked loss of hemispheric tissue (p < 0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.

  • 121. Hanell, Anders
    et al.
    Hedin, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Facilitated assessment of tissue loss following experimental traumatic brain injury2012Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 29, nr 10, s. A154-A154Artikkel i tidsskrift (Annet vitenskapelig)
  • 122.
    Hanrahan, John
    et al.
    Kings Coll London, Fac Life Sci & Med, London WC2R 2LS, England.
    Sideris, Michail
    Queen Mary Univ London, Womens Hlth Res Unit, Mile End Rd, London E1 4NS, England.
    Pasha, Terouz
    Kings Coll London, Fac Life Sci & Med, London WC2R 2LS, England.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Theodoulou, Iakovos
    Kings Coll London, Fac Life Sci & Med, London WC2R 2LS, England.
    Nicolaides, Marios
    Queen Mary Univ London, Barts & London Sch Med & Dent, Mile End Rd, London E1 4NS, England.
    Georgopoulou, Efstratia-Maria
    Univ Athens, Sch Med, Athens 15772, Greece.
    Kombogiorgas, Dimitris
    Metropolitan Hosp, Dept Neurosurg, Athens 18547, Greece.
    Bimpis, Alexios
    Gen Hosp Tripoli, Dept Neurosurg, Erythrou Stavrou Str, Tripoli 22100, Greece.
    Papalois, Apostolos
    Expt Res Ctr ELPEN, Athens, Greece.
    Hands train the brain-what is the role of hand tremor and anxiety in undergraduate microsurgical skills?2018Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, nr 9, s. 1673-1679Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Physiological hand tremor occurs naturally, due to oscillations of the upper extremities. Tremor can be exacerbated by stress and anxiety, interfering with fine motor tasks and potentially impact on surgical performance, particularly in microsurgery. We investigated the link between tremor, anxiety and performance in a neurosurgical module as part of an international surgical course.

    Methods: Essential Skills in the Management of Surgical Cases (ESMSC) course recruits medical students from European Union (EU) medical schools. Students are asked to suture the dura mater in an ex vivo swine model, of which the first suture completed was assessed. Questionnaires were distributed before and after the module, eliciting tremor risk factors, self-perception of tremor and anxiety. Johnson O'Connor dexterity pad was used to objectively measure dexterity. Direct Observation of Procedural Skills (DOPS) was used to assess skills-based performance. Anxiety was assessed using the Westside Test Anxiety Scale (WTAS). Tremor was evaluated by four qualified neurosurgeons.

    Results: Forty delegates participated in the study. Overall performance decreased with greater subjective perception of anxiety (p = 0.032, rho = -0.392). Although increasing scores for tremor at rest and overall WTAS score were associated with decreased performance, this was not statistically significant (p > 0.05). Tremor at rest did not affect dexterity (p = 0.876, rho = -0.027).

    Conclusions: Physiological tremor did not affect student performance and microsurgical dexterity in a simulation-based environment. Self-perception of anxiety affected performance in this module, suggesting that more confident students perform better in a simulated neurosurgical setting.

  • 123.
    Hanrahan, John
    et al.
    Kings Coll London, Fac Life Sci & Med, London SE1 9RT, England.
    Sideris, Michail
    Queen Mary Univ London, Womens Hlth Res Unit, Mile End Rd, London E1 4NS, England.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Bimpis, Alexios
    Gen Hosp Tripoli, Dept Neurosurg, Erythrou Stavrou Odos, Tripoli 22100, Greece.
    Pasha, Terouz
    Kings Coll London, Fac Life Sci & Med, London SE1 9RT, England.
    Whitfield, Peter C.
    Plymouth Hosp NHS Trust, Southwest Neurosurg Ctr, Plymouth PL6 8DH, Devon, England.
    Papalois, Apostolos E.
    Expt Res Ctr ELPEN SA, 95 Marathonos Av, Pikermi 19009, Greece;Expt Res Ctr ELPEN, Athens, Greece.
    Increasing motivation and engagement in neurosurgery for medical students through practical simulation-based learning2018Inngår i: ANNALS OF MEDICINE AND SURGERY, ISSN 2049-0801, Vol. 34, s. 75-79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Simulation-based learning (SBL) is an essential adjunct to modern surgical education. Our study aimed to evaluate the educational benefit and motivational impact of a pilot practical neurosurgical module.

    Materials and methods: 38 clinical medical students from several EU Medical Schools attended an international surgical course focused on teaching and learning basic surgical skills. We designed a pilot neurosurgical workshop instructing students to insert an intracranial pressure bolt using an ex vivo pig model. Each delegate was assessed by two consultant neurosurgeons using a validated assessment tool. Structured questionnaires were distributed on completion of the module.

    Results: Delegate performance increased (p<0.001) with no difference in performance improvement across year of study (p=0.676) or medical school (p=0.647). All delegates perceived this workshop as a potential addition to their education (median 5/5, IQR=0), and indicated that the course provided motivational value towards a neurosurgical career (median 4/5, IQR=1), with no difference seen between year of study or medical school (p>0.05).

    Conclusion: Our pilot neurosurgical workshop demonstrated the educational value of practical SBL learning for motivating students towards a surgical career. Homogeneous views across year of study and medical school underline the value of developing a unified strategy to develop and standardise undergraduate surgical teaching with a practical focus.

  • 124.
    Hanrieder, Jörg
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Temporally resolved differential proteomic analysis of human ventricular CSF for monitoring traumatic brain injury biomarker candidates.2009Inngår i: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 177, nr 2, s. 469-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A shotgun proteomic approach based on nanoflow liquid chromatography (nanoLC) in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI TOF MS/MS) was utilized to quantitatively analyze the protein content of consecutive ventricular cerebrospinal fluid (CSF) samples of severe traumatic brain injury (TBI) patients on an individual basis. CSF was acquired from the lateral ventricle 1–9 days after the TBI incident by canula drain to investigate temporally resolved protein changes in three patients that required intracranial pressure monitoring during neurointensive care. The samples were subjected to at once tryptic digestion followed by isobaric tag labeling before multiplexed peptide separation and MS analysis. By using this approach, we were able to follow characteristic changes in protein concentrations over time allowing new conclusions to be drawn about ongoing pathological processes during TBI. Certain suggested protein-biomarker candidates for TBI, like acute phase reactants (APRs), fibrinogens (FIB), cystatin C (CC) or more brain specific proteins like glial fibrillary acid protein (GFAP) and neuron-specific enolase (NSE) were found to be significantly up-regulated which is in strong consistence with previously reported results. This methodology appears to be a promising tool for studying candidate biomarkers of neurovascular and traumatic brain injuries in the neurointensive care setting.

  • 125.
    Hanslin, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Otterbeck, Alexander
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Miklós, Lipscey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibitionManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Increased plasma lactate in sepsis may not be due to insufficient oxygen

    delivery, but accelerated glycolysis and mitochondrial dysfunction may also contribute. To

    assess critical pathophysiological steps in non-ischemic lactate increase we studied the muscle metabolism with microdialysis in a sepsis model in pigs submitted to continuous E. coli infusion (sepsis group, n=12) for 3 hours (h). A control group (sham group, n=4) underwent the same procedures but did not receive E. coli. Protocolized interventions were applied to normalize oxygen delivery (DO2) and blood pressure. Metabolism was intervened locally via microdialysis catheters with the electron-transport chain inhibitor sodium cyanide and the inhibitor of the major energy consuming enzyme Na+/K+-ATPase ouabain.

    Results: All pigs in the sepsis group had positive blood cultures at 1 h. Median (range) Sequential Organ Failure Assessment (SOFA) score at 0 h was 0 (0-1) in both groups. At 3 h, SOFA increased to 6 (3-6) in the sepsis group but remained virtually unchanged in the sham group. Plasma lactate increased in the sepsis group despite that protocolized interventions maintained DO2.

    Sepsis accelerated glycolysis with a decrease in glucose, maintained or increased in lactate and pyruvate with a virtually normal lactate-to-pyruvate ratio (LPR) in microdialysate from catheters without intervention. The local cyanide intervention produced a severe energy crisis as evidenced by a dramatically elevated LPR, a lowered pyruvate and an increased lactate in both the sepsis and sham group. During sepsis, when the cyanide effect gradually diminished, this energy crisis normalized in the sham group but partly persisted in the sepsis group.

    Conclusions: Our findings suggest a reduction in mitochondrial oxidative capacity induced by sepsis, as revealed by cyanide inhibition. Decreasing energy consumption with a local ouabain intervention did not impact glucose and fat metabolism in sepsis or sham animals.

  • 126.
    Hedlund, Mathilde
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Carlsson, Marianne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Ekselius, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Coping strategies, health-related quality of life and psychiatric history in patients with aneurysmal subarachnoid haemorrhage2010Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 8, s. 1375-1382Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Subarachnoid haemorrhage (SAH) reduces health-related quality of life (HRQoL) and increases the risk of psychiatric sequels such as depression and posttraumatic stress disorder. Especially those with a psychiatric history and those using maladaptive coping strategies are at risk for such sequels. The extent to which HRQoL after SAH was related to a history of psychiatric morbidity and to the use of various coping strategies was assessed.

    Patients admitted to the Uppsala University Hospital with aneurysmal SAH (n = 59) were investigated prospectively. Seven months after SAH, data were collected using the Structured Clinical Interview for DSM-IV axis I disorders, the Short Form-36 (SF-36) Health Survey and the Jalowiec Coping Scale.

    Patients with SAH had lower HRQoL than the general Swedish population in all eight domains of the SF-36. The lower HRQoL was almost entirely in the subgroup with a psychiatric history. HRQoL was also strongly correlated to the use of coping. Physical domains of SF-36 were less affected than mental domains. Those with a psychiatric history used more coping than the remainder with respect to all emotional coping scales. Coping and the presence of a psychiatric history were more strongly related to mental than to physical components of HRQoL.

    A psychiatric history and the use of maladaptive emotional coping were related to worse HRQoL, more to mental than to physical aspects.

  • 127.
    Hedlund, Mathilde
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ekselius, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Carlsson, Marianne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    From monitoring physiological functions to using psychological strategies: Nurses' view of caring for the aneurysmal subarachnoid haemorrhage patient2008Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 17, nr 3, s. 403-411Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: The aims of this study were: (1) to describe nurses' views of the physical and supportive needs of patients who have suffered a subarachnoid haemorrhage (SAH), (2) to describe nurses' views of changes in social circumstances and (3) changes in the mental condition of patients after SAH. BACKGROUND: As patients with SAH are generally younger and predominantly female compared with other stroke groups they may have different needs of nursing support to facilitate adaptation. Caring for persons surviving stroke involves advanced nursing skills such as monitoring neurological functions in neurointensive care and providing physical care during rehabilitation. DESIGN: Explorative descriptive design. METHOD: Semi-structured interviews were performed with 18 nurses in neurointensive and rehabilitation care. A qualitative latent content analysis was conducted. RESULTS: Nurses viewed patients' need for support as a process ranging from highly advanced technological care to 'softer' more emotional care. However, shortages in the communication between neurointesive and rehabilitation nurses regarding this support were acknowledged. Changes in social circumstances and mental conditions were viewed both as obstacles and advantages regarding return to everyday life. Nurses also viewed that the characteristics of the group with SAH was not particularly different from the group with other types of stroke. CONCLUSIONS: Support to patients with SAH is viewed as a process carried out by nurses at neurointensive care units and rehabilitation units. Shortages in communication, regarding this support, were acknowledged. Obstacles and advantages with respect to returning to everyday life could apply to any stroke group, which could make it more difficult for nurses to detect the specific needs of patients with SAH. RELEVANCE TO CLINICAL PRACTICE: The communication between neurointensive nurses and rehabilitation nurses regarding support to patients with SAH is not satisfactory. Occasionally the specific needs of patients with SAH are not recognized.

  • 128.
    Hedlund, Mathilde
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Carlsson, Marianne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Ekselius, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Depression and posttraumatic stress disorder after aneurysmal subarachnoid hemorrhage in relation to lifetime psychiatric morbidity2011Inngår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 25, nr 6, s. 693-700Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction. Little is known about the roles that lifetime psychiatric disorders play in psychiatric and vocational outcomes of aneurysmal subarachnoid haemorrhage (SAH). Materials and methods. Eighty-three SAH patients without apparent cognitive dysfunction were assessed using the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I) after their SAH. Diagnoses were assessed for three time periods, 'lifetime before SAH', '12 months before SAH' and '7 months after SAH'. Results. Forty-five percentage of patients with SAH reported at least one lifetime psychiatric disorder. After SAH, symptoms of depression and/or post-traumatic stress disorder (PTSD) were seen in 41%, more often in those with a psychiatric history prior to SAH (p = 0.001). In logistic regressions, depression after SAH was associated with a lifetime history of major depression, or of anxiety or substance use disorder, as well as with lifetime psychiatric comorbidity. Subsyndromal or full PTSD was predicted by a lifetime history of major depression. After the SAH, 18 patients (22%) had received psychotropic medication and/or psychological treatment, 13 of whom had a disorder. Those with a lifetime history of major depression or treatment with antidepressants before SAH had lower return to work rates than others (p = 0.019 and p = 0.031, respectively). This was also true for those with symptoms of depression and/or PTSD, or with antidepressant treatment after SAH (p = 0.001 and p = 0.031, respectively). Conclusions. Depression and PTSD are present in a substantial proportion of patients 7 months after SAH. Those with a history of psychiatric morbidity, any time before the SAH, are more at risk and also constitute a risk group for difficulties in returning to work.

  • 129.
    Hedlund, Mathilde
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ekselius, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Carlsson, Marianne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Perceived recovery after aneurysmal subarachnoid haemorrhage in individuals with or without depression2010Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 19, nr 11-12, s. 1578-1587Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: The aims of the study were to describe what patients with no or only minor neurological deficits after aneurysmal subarachnoid haemorrhage (SAH) perceived to be important for recovery, and perceived consequences of the illness. BACKGROUND: Quantitative studies indicates unfavourable outcomes after aneurysmal SAH, concerning for example mental health and return to everyday life, among patients expected to recover completely. Thus, it is important to investigate the perceptions of patients and to give them the opportunity to communicate what they consider important for recovery. DESIGN: Qualitative descriptive design. METHOD: Semi-structured interviews with 20 aneurysmal subarachnoid haemorrhagic patients were conducted approximately 12 months after the onset. Analyses were carried out in two steps, beginning with a qualitative content analysis. Due to the findings in the initial content analysis, a structured clinical interview for psychiatric disorders was used as a second step to verify the presence or absence of depression in the participants. RESULTS: Two patterns were identified. One pattern revealed that informants without depression experienced a 'confident perception of recovery', which included perceptions of meaningfulness. Another pattern revealed that depressed informants experienced a 'pessimistic perception of recovery', which included perceptions of hopelessness. Expectations regarding care after departure from the neurointensive care unit were not met. CONCLUSIONS: Individuals suffering from depression after aneurysmal SAH have a pessimistic view of their recovery in contrast to those without depression. These findings highlight the importance of better recognition and treatment of depression in the aftermath of SAH. RELEVANCE TO CLINICAL PRACTICE: These findings highlight the importance of better recognition and treatment of depression after aneurysmal SAH, where nurses play an active role. Nurses should seek to take actions to better meet patient's needs after departure from neurointensive care units.

  • 130.
    Herman, Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Niemelä, Valter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Emami Khoonsari, Payam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sundblom, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 4129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

  • 131.
    Hessington, Amel
    et al.
    Uppsala Univ Hosp, Sect Neurosurg, Dept Neurosci, Uppsala, Sweden.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Aristotle Univ Thessaloniki, Hippokratio Gen Hosp, Thessaloniki, Greece.
    Fahlström, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Favorable clinical outcome following surgical evacuation of deep-seated and lobar supratentorial intracerebral hemorrhage: a retrospective single-center analysis of 123 cases2018Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 160, nr 9, s. 1737-1747Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In spontaneous supratentorial intracerebral hemorrhage (ICH), the role of surgical treatment remains controversial, particularly in deep-seated ICHs. We hypothesized that early mortality and long-term functional outcome differ between patients with surgically treated lobar and deep-seated ICH.

    Method: Patients who underwent craniotomy for ICH evacuation from 2009 to 2015 were retrospectively evaluated and categorized into two subgroups: lobar and deep-seated ICH. The modified Rankin Scale (mRS) was used to evaluate long-term functional outcome.

    Result: Of the 123 patients operated for ICH, 49.6% (n = 61) had lobar and 50.4% (n = 62) deep-seated ICH. At long-term follow-up (mean 4.2 years), 25 patients (20.3%) were dead, while 51.0% of survivors had a favorable outcome (mRS score <= 3). Overall mortality was 13.0% at 30 days and 17.9% at 6 months post-ictus, not influenced by ICH location. Mortality was higher in patients >= 65 years old (p = 0.020). The deep-seated group had higher incidence and extent of intraventricular extension, younger age (52.6 +/- 9.0 years vs. 58.5 +/- 9.8 years; p < 0.05), more frequently pupillary abnormalities, and longer neurocritical care stay (p < 0.05). The proportion of patients with good outcome was 48.0% in deep-seated vs. 54.1% in lobar ICH (p = 0.552). In lobar ICH, independent predictors of long-term outcome were age, hemorrhage volume, preoperative level of consciousness, and pupillary reaction. In deep-seated ICHs, only high age correlated significantly with poor outcome.

    Conclusions: At long-term follow-up, most ICH survivors had a favorable clinical outcome. Neither mortality nor long-term functional outcome differed between patients operated for lobar or deep-seated ICH. A combination of surgery and neurocritical care can result in favorable clinical outcome, regardless of ICH location.

  • 132.
    Hillered, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dahlin, Andreas P
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Chu, Jiangtao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting - a technical approach2014Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, s. 245-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cerebral microdialysis (MD) was introduced as a neurochemical monitoring method in the early 1990s and is currently widely used for the sampling of low molecular weight molecules, signaling energy crisis, and cellular distress in the neurointensive care (NIC) setting. There is a growing interest in MD for harvesting of intracerebral protein biomarkers of secondary injury mechanisms in acute traumatic and neurovascular brain injury in the NIC community. The initial enthusiasm over the opportunity to sample protein biomarkers with high molecular weight cut-off MD catheters has dampened somewhat with the emerging realization of inherent methodological problems including protein-protein interaction, protein adhesion, and biofouling, causing an unstable in vivo performance (i.e., fluid recovery and extraction efficiency) of the MD catheter. This review will focus on the results of a multidisciplinary collaborative effort, within the Uppsala Berzelii Centre for Neurodiagnostics during the past several years, to study the features of the complex process of high molecular weight cut-off MD for protein biomarkers. This research has led to new methodology showing robust in vivo performance with optimized fluid recovery and improved extraction efficiency, allowing for more accurate biomarker monitoring. In combination with evolving analytical methodology allowing for multiplex biomarker analysis in ultra-small MD samples, a new opportunity opens up for high-resolution temporal mapping of secondary injury cascades, such as neuroinflammation and other cell injury reactions directly in the injured human brain. Such data may provide an important basis for improved characterization of complex injuries, e.g., traumatic and neurovascular brain injury, and help in defining targets and treatment windows for neuroprotective drug development.

  • 133.
    Hillered, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Dahlin, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Wetterhall, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hjort, Klas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    New Microdialysis Method for Protein Biomarker Sampling in the Neurointensive Care Setting2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 5, s. A22-A22Artikkel i tidsskrift (Fagfellevurdert)
  • 134.
    Hillered, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nonischemic energy metabolic crisis in acute brain injury2008Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 36, nr 10, s. 2952-2953Artikkel i tidsskrift (Fagfellevurdert)
  • 135. Holmberg, Johan
    et al.
    He, Xiaobing
    Peredo, Inti
    Orrego, Abiel
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ericsson, Christer
    Hovatta, Outi
    Oba-Shinjo, Sueli Mieko
    Nagahashi Marie, Suely Kazue
    Nister, Monica
    Muhr, Jonas
    Activation of Neural and Pluripotent Stem Cell Signatures Correlates with Increased Malignancy in Human Glioma2011Inngår i: PLOS ONE, ISSN 1932-6203, Vol. 6, nr 3, s. e18454-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal-and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.

  • 136.
    Holmström, Ulrika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Aristotle Univ Thessaloniki, Hippokratio Gen Hosp, Thessaloniki, Greece.
    Flygt, Hjalmar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Holtz, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurosurg, Lund, Sweden.
    Neurosurgical untethering with or without syrinx drainage results in high patient satisfaction and favorable clinical outcome in post-traumatic myelopathy patients2018Inngår i: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 56, nr 9, s. 873-882Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study design: Retrospective data collection and patient-reported outcome measures.

    Objectives: To investigate surgical outcome, complications, and patient satisfaction in patients with chronic SCI and symptomatic post-traumatic progressive myelopathy (PPM) who underwent neurosurgical untethering and/or spinal cord cyst drainage with the aim of preventing further neurological deterioration.

    Setting: Single-center study at an academic neurosurgery department.

    Methods: All SCI patients who underwent neurosurgery between 1996 and 2013 were retrospectively included. All medical charts and the treating surgeon's operative reports were reviewed to identify surgical indications, surgical technique, and post-operative complications. A questionnaire and an EQ-5D-instrument were used to assess patient's self-described health status and satisfaction at long-term follow-up.

    Results: Fifty-two patients (43 men, 9 women) were identified, of whom five were dead and one was lost to follow-up. Main indications for surgery were pain (54%), motor (37%), or sensory (8%) impairment, and spasticity (2.0%). Overall complications were rare (8%). At follow-up, the subjectively perceived outcome was improved in 24 and remained unchanged in 21 patients. Thus, the surgical aim was met in 87% of patients. Of the 46 eligible patients, 38 responded to the questionnaire of whom 65% were satisfied with the surgical results. Patients with cervical lesions were more satisfied with the surgical treatment than patients with thoracic/thoracolumbar lesions (p = 0.05).

    Conclusions: Neurosurgical untethering and/or cyst drainage in chronic SCI patients and PPM resulted in a high degree of patient satisfaction, particularly in cervical SCI patients with minimal complications.

  • 137.
    Holtz, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Behandling av akut ryggmärgsskada2009Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 11, s. 757-762Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Behandlingen av akut ryggmärgsskadade patienter har tre huvudmål: minimera det neurologiska bortfallet, påbörja mobiliseringen så snart som möjligt och genomföra adekvat rehabilitering. Varje nyskadad patient måste behandlas som om skadan är reversibel. Målsättningen i det akuta skedet är alltid att rädda neurologisk funktion på såväl ryggmärgs- som rotnivå. Den akuta intensivvårdsbehandlingen har som syfte att motverka de sekundära patofysiologiska händelserna efter ett trauma mot ryggmärgen. Förbättrade rutiner vid omhändertagandet på olycksplatsen och den vård som förmedlas på intensivvårdsavdelningar med specialkompetens inom området utgör de bästa förutsättningarna för att förhindra neurologisk försämring och i bästa fall återvinna neurologisk funktion även om vinsten enbart inskränker sig till ett enda segment.

  • 138.
    Holtz, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Azizi, Mohammad
    Rehabilitativ neurokirurgi2009Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 11, s. 775-778Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Vår ökade erfarenhet av kirurgisk behandling av sena komplikationer efter ryggmärgsskada, benämnd »rehabilitativ neurokirurgi«, medför att patienterna idag kan erbjudas ett flertal olika kirurgiska behandlingar vid smärta och spasticitet, och vid ett tillstånd som benämns posttraumatisk myelopati. Med posttraumatisk myelopati menas en symtombild som karaktäriseras av tilltagande bortfall av motorisk och sensorisk funktion, smärtproblematik, ökad spasticitet, Horners syndrom och ökade besvär med autonom dysreflexi och svettningar. Här presenteras olika kirurgiska alternativ för att mildra effekten av besvär som ytterligare sänker livskvaliteten hos redan hårt drabbade patienter.

  • 139.
    Hopp, Sarah
    et al.
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany.;Univ Hosp Wurzburg, Dept Neurosurg, D-97080 Wurzburg, Germany..
    Albert-Weissenberger, Christiane
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany.;Univ Hosp Wurzburg, Dept Neurosurg, D-97080 Wurzburg, Germany..
    Mencl, Stine
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany..
    Bieber, Michael
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany.;Univ Hosp Wurzburg, Comprehens Heart Failure Ctr DZHI, D-97080 Wurzburg, Germany..
    Schuhmann, Michael K.
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany..
    Stetter, Christian
    Univ Hosp Wurzburg, Dept Neurosurg, D-97080 Wurzburg, Germany..
    Nieswandt, Bernhard
    Univ Wurzburg, Rudolf Virchow Ctr, German Res Soc, Res Ctr Expt Biomed, D-97070 Wurzburg, Germany..
    Schmidt, Peter M.
    CSL Ltd, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic, Australia..
    Monoranu, Camelia-Maria
    Univ Wurzburg, Comprehens Canc Ctr Mainfranken, Inst Pathol, Dept Neuropathol, D-97070 Wurzburg, Germany..
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nolte, Marc W.
    CSL Behring, Marburg, Germany..
    Siren, Anna-Leena
    Univ Hosp Wurzburg, Dept Neurosurg, D-97080 Wurzburg, Germany..
    Kleinschnitz, Christoph
    Univ Hosp Wurzburg, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany..
    Targeting Coagulation Factor XII as a Novel Therapeutic Option in Brain Trauma2016Inngår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 79, nr 6, s. 970-982Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury.

    Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury.

    Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage.

    Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.

  • 140.
    Howells, Tim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Elf, Kristin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Jones, Patricia
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Piper, Ian
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Andrews, Peter
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma2005Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 102, nr 2, s. 311-317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECT: The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP).

    METHODS: A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS). The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult-mostly in the range of 50 to 60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome.

    CONCLUSION: Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.

  • 141.
    Howells, Tim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Johnson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    McKelvey, Tomas
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury2015Inngår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 29, nr 1, s. 97-105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status. The patients studied were a series of 131 traumatic brain injury patients. Pressure reactivity indices were computed in various frequency bands during the first 4 days following injury using bandpass filtering of the input ABP and ICP signals. Patient outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the correlation with GOSe of the mean index value over the first 4 days following injury. Stability of the indices was measured as the mean absolute deviation of the minute by minute index value from 30-min moving averages. The optimal index frequency range for prediction of outcome was identified as 0.018-0.067 Hz (oscillations with periods from 55 to 15 s). The index based on this frequency range correlated with GOSe with rho = -0.46 compared to -0.41 for standard PRx, and reduced the 30-min variation by 23 %.

  • 142.
    Howells, Tim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Johnson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    McKelvey, Tomas
    Chalmers, Dept Signals & Syst, Gothenburg, Sweden..
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The effects of ventricular drainage on the intracranial pressure signal and the pressure reactivity index2017Inngår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, nr 2, s. 469-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In subarachnoid hemorrhage (SAH) patients intracranial pressure (ICP) is usually monitored via an extraventricular drain (EVD), which can produce false readings when the drain is open. It is established that both the ICP cardiac pulse frequency and long term trends over several hours are often seriously corrupted. The aim of this study was to establish whether or not the intermediate frequency bands [respiratory, Mayer wave and very low frequency (VLF)] were also corrupted. The VLF range is of special interest because it is important in cerebral autoregulation studies. Using a pattern recognition algorithm we retrospectively identified 718 cases of EVD opening in 80 SAH patients. An analysis of differences between closed and open-drain periods showed that ICP amplitude decreased significantly in all of the three lower frequency bands when the EVD was open. A similar analysis of systemic arterial pressure signal revealed similar changes in the same frequency bands that were positively correlated with the ICP changes. Therefore we concluded that the changes in the ICP signal represented real, physiological changes and not artifact. Pressure reactivity index (PRx) values were also computed during closed and open-drain periods. We found a small but statistically significant decrease during open-drain periods. Based on analysis of the change in the PRx distribution during open drainage we concluded that this decrease also represented physiological changes rather than artifact. In summary the ICP respiratory, Mayer wave, and VLF frequency bands are not corrupted when the EVD is open, and it safe to use these for autoregulation studies.

  • 143.
    Howells, Tim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    An evaluation of three measures of intracranial compliance in traumatic brain injury patients2012Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, nr 6, s. 1061-1068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To compare intracranial pressure (ICP) amplitude, ICP slope, and the correlation of ICP amplitude and ICP mean (RAP index) as measures of compliance in a cohort of traumatic brain injury (TBI) patients. Mean values of the three measures were calculated in the 2-h periods before and after surgery (craniectomies and evacuations), and in the 12-h periods preceding and following thiopental treatment, and during periods of thiopental coma. The changes in the metrics were evaluated using the Wilcoxon test. The correlations of 10-day mean values for the three metrics with age, admission Glasgow Motor Score (GMS), and Extended Glasgow Outcome Score (GOSe) were evaluated. Patients under and over 60 years old were also compared using the Student test. The correlation of ICP amplitude with systemic pulse amplitude was analyzed. ICP amplitude was significantly correlated with GMS, and also with age for patients 35 years old and older. The correlations of ICP slope and the RAP index with GMS and with age were not significant. All three metrics indicated significant improvements in compliance following surgery and during thiopental coma. None of the metrics were significantly correlated with outcome, possibly due to confounding effects of treatment factors. The correlation of systemic pulse amplitude with ICP amplitude was low ( = 0.18), only explaining 3 % of the variance. This study provides further validation for all three of these features of the ICP waveform as measures of compliance. ICP amplitude had the best performance in these tests.

  • 144.
    Howells, Tim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Smielewski, Peter
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Donnelly, Joseph
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Czosnyka, Marek
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England.;Warsaw Univ Technol, Inst Elect Syst, Warsaw, Poland..
    Hutchinson, Peter J. A.
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Menon, David K.
    Univ Cambridge, Addenbrookes Hosp, Div Anaesthesia, Cambridge, England..
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Aries, Marcel J. H.
    Maastricht Univ, Med Ctr, Dept Crit Care, Maastricht, Netherlands..
    Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols2018Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, nr 3, s. e235-e241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure." Design: Retrospective analysis of prospectively collected data. Setting: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden. Patients: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala. Interventions: None. Measurements and Main Results: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve. Conclusions: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment.

  • 145. Hubers, Anna A M
    et al.
    van Duijn, Erik
    Roos, Raymund A C
    Craufurd, David
    Rickards, Hugh
    Bernhard Landwehrmeyer, G
    van der Mast, Rose C
    Giltay, Erik J
    Suicidal ideation in a European Huntington's disease population.2013Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 151, nr 1, s. 248-58, artikkel-id S0165-0327(13)00472-2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.

    METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.

    RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.

    LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.

    CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.

  • 146.
    Hånell, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Plasticity and Inflammation following Traumatic Brain Injury2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Traumatic Brain Injury (TBI) mainly affects young persons in traffic accidents and the elderly in fall accidents. Improvements in the clinical management have significantly improved the outcome following TBI but survivors still suffer from depression, memory problems, personality changes, epilepsy and fatigue. The initial injury starts a series of events that give rise to a secondary injury process and despite several clinical trials there is no drug available for clinical use that targets secondary brain injury mechanisms. Some recovery of function is seen during the first months following injury but is usually limited and there are no drugs that stimulate the recovery of lost function. Some of the recovery is attributed to plasticity, the brains ability to adapt to new circumstances, and enhancing plasticity via increased axonal growth has the potential to partly restore lost function. In this thesis mice were subjected to the controlled cortical impact model of TBI and functional outcome was evaluated using Morris water maze, the cylinder test and the rotarod. Brain tissue loss was measured in all Papers but the additional histological analyses differ among the Papers. Attempts to increase axonal growth were made by interfering with Nogo receptor function in Paper I and by conditional knockout of ephA4 in Paper II. Contrary to the hypothesis cognition was impaired in Paper I but otherwise no effects of treatment were detected in Paper I and II. Much is still unknown about plasticity and despite the discouraging results of Papers I and II this treatment approach is still worth further exploration. It is firmly established that TBI results in an inflammatory response and some aspects of it may damage brain tissue. In Papers III and IV the inflammatory response was attenuated using an IL-1β directed antibody which resulted in reduced tissue loss and edema while improving cognitive function. The results from Papers III and IV are encouraging and the possibility to find a treatment based on IL-1β inhibition appears promising.

    Delarbeid
    1. Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice
    Åpne denne publikasjonen i ny fane eller vindu >>Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice
    Vise andre…
    2010 (engelsk)Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, nr 7, s. 1297-1309Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutralization of both Nogo-A and MAG improved outcome following TBI in the rat, and neutralization of NgR1 improved outcome following spinal cord injury and stroke in rodent models. However, the behavioral and histological effects of NgR1 inhibition have not previously been evaluated in TBI. We hypothesized that NgR1 negatively influences behavioral recovery following TBI, and evaluated NgR1(-/-) mice (NgR1(-/-) study) and, in a separate study, soluble NgR1 infused intracerebroventricularly immediately post-injury to neutralize NgR1 (sNgR1 study) following TBI in mice using a controlled cortical impact (CCI) injury model. In both studies, motor function, TBI-induced loss of tissue, and hippocampal beta-amyloid immunohistochemistry were not altered up to 5 weeks post-injury. Surprisingly, cognitive function (as evaluated with the Morris water maze at 4 weeks post-injury) was significantly impaired both in NgR1(-/-) mice and in mice treated with soluble NgR1. In the sNgR1 study, we evaluated hippocampal mossy fiber sprouting using the Timm stain and found it to be increased at 5 weeks following TBI. Neutralization of NgR1 significantly increased mossy fiber sprouting in sham-injured animals, but not in brain-injured animals. Our data suggest a complex role for myelin-associated inhibitors in the behavioral recovery process following TBI, and urge caution when inhibiting NgR1 in the early post-injury period.

    Emneord
    cognition, mossy fiber sprouting, NgR(-/-) mice, Nogo-66 receptor, traumatic brain injury
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-135948 (URN)10.1089/neu.2009.1255 (DOI)000280331100014 ()20486800 (PubMedID)
    Tilgjengelig fra: 2010-12-09 Laget: 2010-12-09 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Functional and Histological Outcome following Focal Traumatic Brain Injury in Conditional EphA4-knockout mice
    Åpne denne publikasjonen i ny fane eller vindu >>Functional and Histological Outcome following Focal Traumatic Brain Injury in Conditional EphA4-knockout mice
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-145720 (URN)
    Tilgjengelig fra: 2011-02-10 Laget: 2011-02-10 Sist oppdatert: 2011-05-04
    3. Neutralization of interleukin-1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice
    Åpne denne publikasjonen i ny fane eller vindu >>Neutralization of interleukin-1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice
    Vise andre…
    2009 (engelsk)Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 30, nr 3, s. 385-396Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.

    sted, utgiver, år, opplag, sider
    Federation of European Neuroscience Societies and Blackwell Publishing Ltd, 2009
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-107781 (URN)10.1111/j.1460-9568.2009.06820.x (DOI)000268654900005 ()19614750 (PubMedID)
    Tilgjengelig fra: 2009-08-26 Laget: 2009-08-26 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Neutralization of Interleukin-1β Reduces Cerebral Edema and Tissue loss and Improves Late Cognitive Outcome Following Traumatic Brain Injury in Mice
    Åpne denne publikasjonen i ny fane eller vindu >>Neutralization of Interleukin-1β Reduces Cerebral Edema and Tissue loss and Improves Late Cognitive Outcome Following Traumatic Brain Injury in Mice
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-145721 (URN)
    Tilgjengelig fra: 2011-02-10 Laget: 2011-02-10 Sist oppdatert: 2011-05-04
  • 147.
    Hånell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Björk, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Jansson, Kristine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Philipson, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nilsson, Lars N. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Weinreb, Paul H.
    Lee, Daniel
    McIntosh, Tracy K.
    Gimbel, David A.
    Strittmatter, Stephen M.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice2010Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 27, nr 7, s. 1297-1309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutralization of both Nogo-A and MAG improved outcome following TBI in the rat, and neutralization of NgR1 improved outcome following spinal cord injury and stroke in rodent models. However, the behavioral and histological effects of NgR1 inhibition have not previously been evaluated in TBI. We hypothesized that NgR1 negatively influences behavioral recovery following TBI, and evaluated NgR1(-/-) mice (NgR1(-/-) study) and, in a separate study, soluble NgR1 infused intracerebroventricularly immediately post-injury to neutralize NgR1 (sNgR1 study) following TBI in mice using a controlled cortical impact (CCI) injury model. In both studies, motor function, TBI-induced loss of tissue, and hippocampal beta-amyloid immunohistochemistry were not altered up to 5 weeks post-injury. Surprisingly, cognitive function (as evaluated with the Morris water maze at 4 weeks post-injury) was significantly impaired both in NgR1(-/-) mice and in mice treated with soluble NgR1. In the sNgR1 study, we evaluated hippocampal mossy fiber sprouting using the Timm stain and found it to be increased at 5 weeks following TBI. Neutralization of NgR1 significantly increased mossy fiber sprouting in sham-injured animals, but not in brain-injured animals. Our data suggest a complex role for myelin-associated inhibitors in the behavioral recovery process following TBI, and urge caution when inhibiting NgR1 in the early post-injury period.

  • 148.
    Hånell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Nylund, Anders
    Vallstedt, Anna
    Israelsson, Charlotte
    Larhammar, Dan
    Björk, Maria
    Kullander, Klas
    Marklund, Niklas
    Functional and Histological Outcome following Focal Traumatic Brain Injury in Conditional EphA4-knockout miceManuskript (preprint) (Annet vitenskapelig)
  • 149.
    Hånell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Structured evaluation of rodent behavioral tests used in drug discovery research2014Inngår i: Frontiers in Behavioral Neuroscience, ISSN 1662-5153, E-ISSN 1662-5153, Vol. 8Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    A large variety of rodent behavioral tests are currently being used to evaluate traits such as sensory-motor function, social interactions, anxiety-like and depressive-like behavior, substance dependence and various forms of cognitive function. Most behavioral tests have an inherent complexity, and their use requires consideration of several aspects such as the source of motivation in the test, the interaction between experimenter and animal, sources of variability, the sensory modality required by the animal to solve the task as well as costs and required work effort. Of particular importance is a test's validity because of its influence on the chance of successful translation of preclinical results to clinical settings. High validity may, however, have to be balanced against practical constraints and there are no behavioral tests with optimal characteristics. The design and development of new behavioral tests is therefore an ongoing effort and there are now well over one hundred tests described in the contemporary literature. Some of them are well established following extensive use, while others are novel and still unproven. The task of choosing a behavioral test for a particular project may therefore be daunting and the aim of the present review is to provide a structured way to evaluate rodent behavioral tests aimed at drug discovery research.

  • 150.
    Högberg, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Meurling, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Stenbäck, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Intestinal ischemia measured by intraluminal microdialysis2012Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, nr 1, s. 59-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective.

    To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon.

    Methods.

    The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation.

    Results.

    Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage.

    Conclusion.

    Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.

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