Camara-Lemarroy, CarlosTottenham, Isabelle Elaine Louise2023-09-282023-09-282023-09-20Tottenham, I. E. L. (2023). Repurposing repeated remote ischemic postconditioning for multiple sclerosis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/117175https://doi.org/10.11575/PRISM/42017Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease that is characterized by nervous system demyelination and heterogenous disability. Current disease modifying treatments accessible to Canadians are limited because they are primarily targeting the neuroinflammatory component of the disease, not the neurodegenerative component. There is a need for focus on development of therapies that target the demyelinating insults that people with MS experience. In this study, we evaluate the use of repeated remote ischemic postconditioning (RIC) as a therapeutic target for promoting white matter repair and protection. Due to the novelty of the intervention in the MS field, we first wanted to identify transcriptomic and proteomic changes to the spinal cord with repeated RIC. We found that targets involved in antioxidant, protein synthesis, angiogenesis, axonogenesis, and remyelination pathways (among others) were upregulated with 14 days of consecutive RIC. Using a focal demyelinating mouse model, we also described changes to the lesion environment using the repeated intervention. Repeated RIC did not reduce the lesion size in this injury model. However, targets such as plectin and neurofascin that were upregulated in the transcriptomic and proteomic data sets were also upregulated in the lesion of animals that received treatment. An increase in myelin in the lesion area was also found in the repeated RIC group when compared to sham. Overall, repeated RIC demonstrates potential for future use as a therapy to target white matter repair and protection.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.multiple sclerosisremyelinationremote ischemic conditioningremote ischemic postconditioninghypoxiaoligodendrocyteoligodendrocyte precursor cellneuroprotectionneurorepairNeurosciencemaster thesis