Novel Strategy to Protect and Induce Repair in Experimental Autoimmune Encephalomyelitis (EAE)
| dc.contributor.advisor | Verge, Valerie | |
| dc.contributor.committeeMember | Levin, Michael | |
| dc.contributor.committeeMember | Popescu, Bogdan | |
| dc.contributor.committeeMember | Donkers, Sarah | |
| dc.creator | Tokarska, Nataliya | |
| dc.date.accessioned | 2020-10-05T15:39:00Z | |
| dc.date.available | 2023-10-15T06:05:08Z | |
| dc.date.created | 2020-11 | |
| dc.date.issued | 2020-10-05 | |
| dc.date.submitted | November 2020 | |
| dc.date.updated | 2020-10-05T15:39:01Z | |
| dc.description.abstract | Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that is characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration. Efficient repair of demyelinated lesions is one of the major challenges of MS. Conventional therapeutic approaches tend to focus on modulation of the immune response responsible for the generation of these lesions. While this may help to alleviate some symptoms and mitigate damage, immune system modulation alone does not tackle the fundamental problem of remyelinating the damaged areas of the nervous system. In MS, demyelination can be followed early on by efficient remyelination, supporting that endogenous repair mechanisms exist. Our lab focuses on therapies that enhance intrinsic repair mechanisms of the injured nervous system. We find that acute intermittent hypoxia (AIH; intermittent periods of reduced oxygen), a non-invasive therapy, improves outcomes in spinal cord and peripheral nerve injured animals, the latter in a manner akin to electrical stimulation, likely due to AIH’s ability to increase neural activity. But its potential for repair in MS is unknown. We hypothesized that AIH treatment would enhance repair of the demyelinated CNS and mitigate experimental autoimmune encephalomyelitis (EAE) disease progression in the MOG35- 55 EAE mouse model of MS. AIH or Normoxia control treatments were administered either at onset of EAE disease (score = 1) or at near peak EAE disease (score = 2.5) once daily for 7 days, with EAE mice followed for an additional 7 days post-treatment. Animals were examined daily for changes in clinical scores and spinal cord tissue at the end of clinical score analysis was processed for immunofluorescence to assess the impact that AIH treatment has on the degree of myelination, axonal integrity, oligodendrocyte precursor cell (OPC) recruitment, and immune response modulation. Analysis of clinical scores showed that 7 days of daily AIH treatment significantly improved clinical scores when treatment was started at near peak EAE disease but showed no significant changes when started at onset of disease. AIH treatment at near peak of disease, as compared to the Normoxia treatment group, resulted in significantly elevated levels of myelin basic protein (MBP), axon protective phosphorylated neurofilaments, reorganization of node of Ranvier Caspr+ve paranodes and OPC recruitment. I also observed a quicker resolution of the inflammatory response and the polarization of macrophages/microglia toward a pro-repair M2 phenotype. Collectively, these findings support a role for AIH treatment as a non-invasive therapeutic strategy to enhance CNS repair following demyelination. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/10388/13082 | |
| dc.subject | Multiple Sclerosis | |
| dc.subject | Experimental Autoimmune Encephalomyelitis | |
| dc.subject | EAE | |
| dc.subject | Acute Intermittent Hypoxia | |
| dc.subject | AIH | |
| dc.subject | Myelin | |
| dc.subject | Repair | |
| dc.subject | Remyelination | |
| dc.title | Novel Strategy to Protect and Induce Repair in Experimental Autoimmune Encephalomyelitis (EAE) | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.terms | 2023-10-15 | |
| thesis.degree.department | Anatomy and Cell Biology | |
| thesis.degree.discipline | Anatomy and Cell Biology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |