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Sköld, Mattias K.
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Publications (8 of 8) Show all publications
Bergen, K., Frodin, M., von Gertten, C., Sandberg-Nordqvist, A.-C. -. & Sköld, M. K. (2018). Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment. Brain Sciences, 8(8), Article ID 151.
Open this publication in new window or tab >>Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment
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2018 (English)In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 8, no 8, article id 151Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MDPI, 2018
Keywords
IGF-1, IGFBP-2, vitronectin, in vitro trauma, regeneration, hippocampal neuron
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-364051 (URN)10.3390/brainsci8080151 (DOI)000443165900014 ()30103517 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Sköld, M. K. & Fehlings, M. G. (2017). Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System: An Update on Recent Advances in Regenerative Neuroscience. Frontiers in Neurology, 8, Article ID 510.
Open this publication in new window or tab >>Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System: An Update on Recent Advances in Regenerative Neuroscience
2017 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 510Article in journal, Editorial material (Other academic) Published
Keywords
spinal cord injuries, brachial plexus injury, neuronal regeneration, nerve injury, neuronal plasticity and repair
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-346550 (URN)10.3389/fneur.2017.00510 (DOI)000411758100001 ()
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Lindholm, T., Risling, M., Carlstedt, T., Hammarberg, H., Wallquist, W., Cullheim, S. & Sköld, M. K. (2017). Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury. Frontiers in Neurology, 8, Article ID 49.
Open this publication in new window or tab >>Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury
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2017 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, article id 49Article in journal (Refereed) Published
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.

Keywords
rhizothomy, DRG, regeneration, semaphorins, neuropilins, VEGF
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-317941 (URN)10.3389/fneur.2017.00049 (DOI)000394339300001 ()28270793 (PubMedID)
Available from: 2017-04-01 Created: 2017-04-01 Last updated: 2018-01-13Bibliographically approved
Cao, Y., Risling, M., Malm, E., Sonden, A., Bolling, M. F. & Sköld, M. K. (2016). Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types. Frontiers in Neurology, 7, Article ID UNSP 10.
Open this publication in new window or tab >>Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types
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2016 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, article id UNSP 10Article in journal (Refereed) Published
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.

Keywords
in vitro high-energy cavitation trauma model, flyer-plate, automatic time-lapse imaging, neuroblastoma, glioma, post trauma mechanisms, mitosis, regulated differential gene expression
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-281843 (URN)10.3389/fneur.2016.00010 (DOI)000370431600002 ()26869990 (PubMedID)
Available from: 2016-04-06 Created: 2016-03-30 Last updated: 2017-11-30Bibliographically approved
Agoston, D. V. & Sköld, M. K. (2016). Editorial: When Physics Meets Biology; Biomechanics and Biology of traumatic Brain injury. Frontiers in Neurology, 7, Article ID 91.
Open this publication in new window or tab >>Editorial: When Physics Meets Biology; Biomechanics and Biology of traumatic Brain injury
2016 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 7, article id 91Article in journal, Editorial material (Other academic) Published
Keywords
physics, forces, biology, response, brain
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-300132 (URN)10.3389/fneur.2016.00091 (DOI)000377746400001 ()
Available from: 2016-08-03 Created: 2016-08-03 Last updated: 2017-11-28Bibliographically approved
Sköld, M. & Gunther, M. (2016). Ventral root avulsion and replantation - description of different gene expression patterns in acute and delayed replantation. Paper presented at 12th Symposium of the International-Neurotrauma-Society, FEB 01-04, 2016, Cape Town, SOUTH AFRICA. Journal of Neurotrauma, 33(3), A12-A13
Open this publication in new window or tab >>Ventral root avulsion and replantation - description of different gene expression patterns in acute and delayed replantation
2016 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, no 3, p. A12-A13Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-301737 (URN)000369513600035 ()
External cooperation:
Conference
12th Symposium of the International-Neurotrauma-Society, FEB 01-04, 2016, Cape Town, SOUTH AFRICA
Available from: 2016-08-25 Created: 2016-08-24 Last updated: 2017-11-28Bibliographically approved
Cao, Y., Sköld, M. K., Malm, E., Sonden, A. & Risling, M. (2014). Hypothermia and in Vitro High-Energy Trauma. Paper presented at 32nd Annual National Neurotrauma Symposium, JUN 29-JUL 02, 2014, San Francisco, CA. Journal of Neurotrauma, 31(12), A105-A105
Open this publication in new window or tab >>Hypothermia and in Vitro High-Energy Trauma
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2014 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 31, no 12, p. A105-A105Article in journal, Meeting abstract (Other academic) Published
Keywords
automatic cell incubation, gene array microarray, gene expression regulation, high energy in vitro trauma, human neuroblastoma cells (SH-SY5Y), hypothermia, image-analysis, imaging
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-229608 (URN)000338443600285 ()
Conference
32nd Annual National Neurotrauma Symposium, JUN 29-JUL 02, 2014, San Francisco, CA
Available from: 2014-08-12 Created: 2014-08-12 Last updated: 2018-01-11Bibliographically approved
Howells, T., Lewen, A., Sköld, M. K., Ronne-Engström, E. & Enblad, P. (2012). An evaluation of three measures of intracranial compliance in traumatic brain injury patients. Intensive Care Medicine, 38(6), 1061-1068
Open this publication in new window or tab >>An evaluation of three measures of intracranial compliance in traumatic brain injury patients
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2012 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, no 6, p. 1061-1068Article in journal (Refereed) Published
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.

Keywords
Intracranial compliance, Traumatic brain injury, Intracranial pressure, Cerebral hemodynamics
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-176216 (URN)10.1007/s00134-012-2571-7 (DOI)000304143100018 ()
Available from: 2012-06-19 Created: 2012-06-18 Last updated: 2017-12-07Bibliographically approved
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