IMPACT OF BRIEF ELECTRICAL STIMULATION ON PERIPHERAL NERVE REMYELINATION
| dc.contributor.committeeMember | Verge, Valerie | |
| dc.contributor.committeeMember | Krone, Patrick | |
| dc.contributor.committeeMember | Popescu, Bogdan | |
| dc.contributor.committeeMember | Nichol, Helen | |
| dc.contributor.committeeMember | Knox, Katherine | |
| dc.creator | McLean, Nikki 1982- | |
| dc.date.accessioned | 2020-02-11T20:48:29Z | |
| dc.date.available | 2020-02-11T20:48:29Z | |
| dc.date.created | 2015-12 | |
| dc.date.submitted | December 2015 | |
| dc.date.updated | 2020-02-11T20:48:29Z | |
| dc.description.abstract | Demyelinating diseases such as Guillain-Barré syndrome are characterized by segmental axon demyelination and infiltration by cells of the monocyte lineage. Destruction of the myelin sheath is accompanied by losses of phosphorylated neurofilament proteins and node of Ranvier protein organization, impairing axon function and health. Effective repair depends on clearance of myelin debris, reorganization of the nodal proteins, resolution of the inflammatory response as well as increased expression of a molecule involved in myelination, brain-derived neurotrophic factor (BDNF). Brief electrical stimulation (ES) of transected and repaired peripheral nerves has been shown to enhance remyelination, and also elevate neuronal BDNF expression, the latter raising the question about whether ES might be an effective therapeutic intervention for repair of nerves following a focal demyelinating insult. To examine this, adult male Wistar rat tibial nerves underwent unilateral focal demyelination via injection of 1% lysophosphatidyl choline just distal to the sciatic nerve trifurcation. Five days later, the sciatic nerve in half of the animals underwent 1 hour continuous 20 Hz ES proximal to the injection site. At various time points after ES, animals were euthanized and ipsilateral and contralateral nerves were processed to examine the impact of stimulation on the degree of remyelination, axonal integrity, glial reactivity and the immune response. Stimulated nerves displayed greater demyelination, increased BDNF expression at the lesion site, and a decrease in local Schwann cell reactivity. The stimulated axons also displayed important markers of axonal health - increased phosphorylated neurofilament expression and a re-formation of node of Ranvier Caspr/Kv1.2 protein clusters. The ES procedure had a remarkable impact on the inflammatory/immune response, enhancing debris clearance, decreasing the total number of macrophages present and shifting macrophage phenotype from a pro-inflammatory (M1) to a pro-repair (M2) one. Collectively these results support that ES not only helps to create an environment permissive for early remyelination, but also does so by promoting the protection and preservation of axons and favorably altering the immune response. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/10388/12605 | |
| dc.subject | Myelin | |
| dc.subject | Schwann cell | |
| dc.subject | demyelination | |
| dc.subject | lysophosphatidyl choline | |
| dc.subject | macrophage | |
| dc.title | IMPACT OF BRIEF ELECTRICAL STIMULATION ON PERIPHERAL NERVE REMYELINATION | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Anatomy and Cell Biology | |
| thesis.degree.discipline | Anatomy and Cell Biology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |