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  • 1. Kong, Wan-Yee
    et al.
    Tan, Benjamin Y Q
    Ngiam, Nicholas J H
    Tan, Deborah Y C
    Yuan, Christine H
    Holmin, Staffan
    Andersson, Tommy
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Teoh, Hock Luen
    Chan, Bernard P L
    Rathakrishnan, Rahul
    Ting, Eric Y S
    Sharma, Vijay K
    Yeo, Leonard L L
    Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.2017In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 26, no 10, p. 2264-2271, article id S1052-3057(17)30227-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value.

    METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more.

    RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001).

    CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.

  • 2.
    Kragsterman, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Carotid Endarterectomy Induces the Release of Inflammatory Markers and the Activation of Coagulation as Measured in the Jugular Bulb2017In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 26, no 10, p. 2320-2328Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Transient cerebral hypoxia may induce neuronal injury through an ischemia-reperfusion (I/R) response, with a subsequent activation of inflammation and coagulation-fibrinolysis. During carotid endarterectomy (CEA), the artery is clamped, which might impair the regional cerebral perfusion and initiate a local I/R response. Data suggest that the CD40-CD40 ligand dyad acts as a modulator in the induced activation. The aim of this study was to locally measure soluble CD40 ligand (sCD40L), in conjunction with inflammation and coagulation activation markers, during CEA.

    Subjects and Methods: This is a prospective study of 18 patients undergoing CEA. Blood samples from the venous jugular bulb (JB) and the radial artery (RA) were drawn at baseline and during the procedure. Measurements of sCD40L, interleukin-6 (IL-6), fragment 1 + 2 (F1 + 2), plasminogen activator inhibitor-1 (PAI-1), and D-dimer were analyzed. Comparisons during CEA were made between levels: baselines versus JB, JB versus RA, and sequential JB measurements. Fifty cardiovascular healthy patients were the reference group for the sCD40L baseline comparison.

    Results: Increased cerebral IL-6 levels were demonstrated throughout the procedure, as well as the temporal influence in F1 + 2, PAI-1, and D-dimer values. sCD40L remained unchanged throughout the procedure. This indicates a local cerebral inflammatory reaction together with an activation of coagulation-fibrinolysis, but it does not appear to primarily involve the CD40-CD40 ligand dyad.

    Conclusions: Signs of a local inflammatory reaction and activation of coagulation were observed during CEA, but levels of sCD40L remained stable, unaffected by carotid artery clamping and reperfusion.

  • 3.
    Kucuk, Mutlu
    et al.
    Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Lab Anim Sci, Istanbul, Turkey.
    Yilmaz, Canan Ugur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Lab Anim Sci, Istanbul, Turkey.
    Orhan, Nurcan
    Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Neurosci, Istanbul, Turkey.
    Ahishali, Bulent
    Istanbul Univ, Istanbul Fac Med, Dept Histol & Embryol, Istanbul, Turkey.
    Arican, Nadir
    Istanbul Univ, Istanbul Fac Med, Dept Forens Med, Istanbul, Turkey.
    Elmas, Imdat
    Istanbul Univ, Istanbul Fac Med, Dept Forens Med, Istanbul, Turkey.
    Gürses, Candan
    Koc Univ, Sch Med, Dept Neurol, Istanbul, Turkey.
    Kaya, Mehmet
    Koc Univ, Sch Med, Dept Physiol, Istanbul, Turkey.
    The Effects of Lipopolysaccharide on the Disrupted Blood-Brain Barrier in a Rat Model of Preeclampsia2018In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, no 12, p. 3411-3418Article in journal (Refereed)
    Abstract [en]

    Background: Preeclampsia is a disorder characterized by high blood pressure and often proteinuria during pregnancy. It is known that a subseptic dose of bacterial lipopolysaccharide (LPS) induces production of proinflammatory cytokines, and possibly increasing the risk for developing preeclampsia. We investigated the effects of LPS on the blood-brain barrier (BBB) integrity in pregnant rats with N (omega)-nitro-L-arginine methyl ester (L-NAME) induced preeclampsia.

    Methods: Starting from the 10th day of gestation, pregnant rats were given L-NAME for 10 days to produce hypertension and proteinuria. Animals were then treated with a single injection of LPS on the 19th day of pregnancy. Arterial blood pressure and proteinuria were measured on the day of the experiment, which was 24 hours after the LPS injection. The BBB integrity was assessed by using Evans blue (EB) and horseradish peroxidase (HRP) tracers.

    Results: Proteinuria was observed in varying degrees, and the arterial blood pressure increased in L-NAME-treated pregnant rats (P < .01). The overall brain EB content did not increase in these preeclamptic rats when compared to pregnant animals, and LPS treatment also did not change EB content. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in the capillary endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated with L-NAME (P < .01). However, LPS did not change the amounts of HRP that mainly accumulated in brain capillary endothelial cells of these animals.

    Conclusion: Our results suggest that, in this experimental setting, LPS does not change the severity of BBB disruption observed in preeclamptic animals.

  • 4.
    Lindblom, Rickard P F
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Molnar, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Israelsson, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Röjsäter, Belinda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest2018In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, no 5, p. 1200-1211Article in journal (Refereed)
    Abstract [en]

    Background: Survivors of cardiac arrest often experience neurologic deficits. To date, treatment options are limited. Associated hyperglycemia is believed to further worsen the neurologic outcome. The aim with this study was to characterize expression pathways induced by hyperglycemia in conjunction with global brain ischemia.

    Methods: Pigs were randomized to high or normal glucose levels, as regulated by glucose and insulin infusions with target levels of 8.5-10 mM and 4-5.5 mM, respectively. The animals were subjected to 5-minute cardiac arrest followed by 8 minutes of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Global expression profiling of the cortex using microarrays was performed in both groups.

    Results: A total of 102 genes differed in expression at P<.001 between the hyperglycemic and the normoglycemic pigs. Several of the most strongly differentially regulated genes were involved in transport and metabolism of glucose. Functional clustering using bioinformatics tools revealed enrichment of multiple biological processes, including membrane processes, ion transport, and glycoproteins.

    Conclusions: Hyperglycemia during cardiac arrest leads to differential early gene expression compared with normoglycemia. The functional relevance of these expressional changes cannot be deduced from the current study; however, the identified candidates have been linked to neuroprotective mechanisms and constitute interesting targets for further studies.

  • 5.
    Nylander, Ruta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population2015In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 24, no 2, p. 312-318Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.

    METHODS:

    Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.

    RESULTS:

    One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.

    CONCLUSIONS:

    The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.

  • 6.
    Vahlberg, Birgit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Zetterberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Factors Related to Performance-Based Mobility and Self-reported Physical Activity in Individuals 1-3 Years after Stroke: A Cross-sectional Cohort Study2013In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 22, no 8, p. E426-E434Article in journal (Refereed)
    Abstract [en]

    Background: Low mobility and low level of physical activity is common after stroke. The objective of this study was to relate these outcomes to physical, psychological, and demographic determinants. Methods: In this cross-sectional cohort study, a consecutive sample of 195 community-living individuals, 65-85 years of age (74 +/- 5 years, 71% men) with a previous stroke was included. Exclusion criteria were severe aphasia and severe cognitive dysfunction. Mobility status was measured by the Short Physical Performance Battery (SPPB, 0-12 points), and physical activity was measured using the Physical Activity Scale for the Elderly (PASE). Results: Mobility (SPPB, median 9 points) and level of physical activity were low (mean PASE 97 +/- 66 points), and walking speed was slow (1.10 +/- .86 m/s), in relation to a healthy population-based sample. In multiple regression analyses, age (P = .001), physical activity (P < .001), fall-related self-efficacy (P = .001), and health-related quality of life (HRQoL) (P = .02) were associated with mobility (SPPB). Mobility (P < .001), HRQoL (P = .014), and fall-related self-efficacy (P = .031) were likewise associated with self-reported physical activity as the dependent variable. The regression models described 42% and 31% of the variance in mobility and physical activity, respectively. Conclusions: Individuals perceived disabilities that are partly potentially modifiable 1-3 years after stroke. Future poststroke rehabilitation studies need to evaluate if actions to improve fall-related self-efficacy and mobility could promote the physical activity level in this patient population.

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