| 1. |
- Nordblom, Jonathan, et al.
(författare)
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FGF1 containing biodegradable device with peripheral nerve grafts induces corticospinal tract regeneration and motor evoked potentials after spinal cord resection
- 2012
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 30:2, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1.Methods: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry including anterograde BDA tracing.Results: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals.Conclusions: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research.
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| 2. |
- Fagerlund, Michael, et al.
(författare)
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Proliferation, migration and differentiation of ependymal region neural progenitor cells in the brainstem after hypoglossal nerve avulsion
- 2011
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Ingår i: Restorative Neurology and Neuroscience. - 1878-3627. ; 29:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cells in the ependymal region in the adult central nervous system (CNS) have been found to possess neural progenitor cell (NPC) like features including capacity for generating new neurons and glia in response to injury and inflammatory disease. Whether these cells are activated after a peripheral nerve injury has not previously been extensively evaluated. Methods: We investigate the possible activation and effect of NPCs in the ependymal region in the immediate vicinity to the hypoglossal nucleus in the brainstem using two models of injuries, hypoglossal nerve transection and nerve avulsion after which the proliferation, migration and differentiation of ependymal regional NPCs were evaluated. Results: We showed that: (i) immunoreactivity for Sox2 was detected in cells in the ependymal region of the brainstem and that BrdU/Sox2-positive cells were observed after avulsion, but not after transection injury; (ii) avulsion induces re-expression of nestin in the ependymal layer as well as induced NPC migration from the ependymal layer; (iii) the chemokine SDF-1 alpha (a marker for migrating cells) was upregulated ipsilateral to the nerve injury; (iiii) the NPCs migrating differentiated only into GFAP-positive astrocytes in the hypoglossal nucleus. Conclusion: These results suggest that nerve avulsion injury induces in parallel with the retrograde "axon reaction" activation of endogenous NPCs in the ependymal region and further suggest that these cells could be involved in repair and neuroregeneration after injury within the brainstem.
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| 3. |
- Covacu, Ruxandra, et al.
(författare)
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Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis
- 2006
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 178, s. 268-268
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and beta-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.
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