Repurposing repeated remote ischemic postconditioning for multiple sclerosis
Date
2023-09-20
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Multiple 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.
Description
Keywords
multiple sclerosis, remyelination, remote ischemic conditioning, remote ischemic postconditioning, hypoxia, oligodendrocyte, oligodendrocyte precursor cell, neuroprotection, neurorepair
Citation
Tottenham, 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.