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  • 1.
    Agoston, Denes V.
    et al.
    Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA.;Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Editorial: When Physics Meets Biology; Biomechanics and Biology of traumatic Brain injury2016Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, artikkel-id 91Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Bergen, K.
    et al.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
    Frodin, M.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
    von Gertten, C.
    Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
    Sandberg-Nordqvist, A. -C
    Department of Clinical Neuroscience, Karolinska Institutet.
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
    Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment2018Inngår i: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 8, nr 8, artikkel-id 151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Following traumatic brain injuries (TBI), insulin-like growth factor (IGF) is cortically widely upregulated. This upregulation has a potential role in the recovery of neuronal tissue, plasticity, and neurotrophic activity, though the molecular mechanisms involved in IGF regulation and the exact role of IGF after TBI remain unclear. Vitronectin (VN), an extracellular matrix (ECM) molecule, has recently been shown to be of importance for IGF-mediated cellular growth and migration. Since VN is downregulated after TBI, we hypothesized that insufficient VN levels after TBI impairs the potential beneficial activity of IGF. To test if vitronectin and IGF-1/IGFBP-2 could contribute to neurite growth, we cultured hippocampal neurons on +/- vitronectin-coated coverslips and them treated with +/- IGF-1/IGF binding protein 2 (IGFBP-2). Under same conditions, cell cultures were also subjected to in vitro trauma to investigate differences in the posttraumatic regenerative capacity with +/- vitronectin-coated coverslips and with +/- IGF-1/IGFBP-2 treatment. In both the control and trauma situations, hippocampal neurons showed a stronger growth pattern on vitronectin than on the control substrate. Surprisingly, the addition of IGF-1/IGFBP-2 showed a decrease in neurite growth. Since neurite growth was measured as the number of neurites per area, we hypothesized that IGF-1/IGFBP-2 contributes to the polarization of neurons and thus induced a less dense neurite network after IGF-1/IGFBP-2 treatment. This hypothesis could not be confirmed and we therefore conclude that vitronectin has a positive effect on neurite growth in vitro both under normal conditions and after trauma, but that addition of IGF-1/IGFBP-2 does not have a positive additive effect.

  • 3. Cao, Y.
    et al.
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Malm, E.
    Sonden, A.
    Risling, M.
    Hypothermia and in Vitro High-Energy Trauma2014Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, nr 12, s. A105-A105Artikkel i tidsskrift (Annet vitenskapelig)
  • 4.
    Cao, Yuli
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Risling, Marten
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Malm, Elisabeth
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sonden, Anders
    Karolinska Inst Sodersjukhuset, Dept Clin Sci & Educ, Sect Surg, Stockholm, Sweden..
    Bolling, Magnus Frödin
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types2016Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, artikkel-id UNSP 10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mechanisms involved in traumatic brain injury have yet to be fully characterized. One mechanism that, especially in high-energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation, and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer-plate model is an in vitro high-energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation, and shock waves inside the well and cell medium. We have found the flyer-plate model to be efficient, reproducible, and easy to control. In this study, we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose-dependent manner. Using gene expression microarray, a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 h post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies.

  • 5.
    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.

  • 6.
    Lindholm, Tomas
    et al.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Helsa Foretagshalsovard Ostermalm, Stockholm, Sweden..
    Risling, Marten
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Carlstedt, Thomas
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;UCL, Hammersmith Hosp, London WC1E 6BT, England.;Imperial Coll, London, England.;Soder Sjukhuset, Dept Hand Surg, Stockholm, Sweden.;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Hammarberg, Henrik
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Soder Sjukhuset, Dept Hand Surg, Stockholm, Sweden.;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden..
    Wallquist, Wilhelm
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden.;Vasteras Gen Hosp, Dept Anesthesiol & Intens Care, Vasteras, Sweden..
    Cullheim, Staffan
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Sköld, Mattias K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury2017Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, artikkel-id 49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.

  • 7.
    Sköld, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, S-10401 Stockholm, Sweden.
    Gunther, M.
    Karolinska Inst, S-10401 Stockholm, Sweden.
    Ventral root avulsion and replantation - description of different gene expression patterns in acute and delayed replantation2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A12-A13Artikkel i tidsskrift (Annet vitenskapelig)
  • 8.
    Sköld, Mattias K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Fehlings, Michael G.
    Univ Toronto, Dept Neurosurg, Toronto, ON, Canada.;Toronto Western Hosp, Spine Program, Toronto, ON, Canada..
    Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System: An Update on Recent Advances in Regenerative Neuroscience2017Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, artikkel-id 510Artikkel i tidsskrift (Annet vitenskapelig)
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