Investigating the relationship between the immune response and ependymoglial activation during spinal cord regeneration in the adult and juvenile zebrafish model

dc.contributor.authorTrzuskot, Lidia
dc.contributor.examiningcommitteeKarimi, Soheila (Physiology and Pathophysiology)en_US
dc.contributor.examiningcommitteeLogue, Susan (Human Anatomy and Cell Science)en_US
dc.contributor.supervisorLindsey, Benjamin
dc.date.accessioned2022-04-05T15:07:37Z
dc.date.available2022-04-05T15:07:37Z
dc.date.copyright2022-03-29
dc.date.issued2022-03-29
dc.date.submitted2022-03-29T21:53:15Zen_US
dc.degree.disciplineHuman Anatomy and Cell Scienceen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractSpinal cord injury (SCI) is a life changing condition affecting individuals within Canada and worldwide with no effective treatment to date. A limitation in humans, like other mammals, is that they cannot repair the damaged central nervous system after injury. By contrast, the zebrafish model has a remarkable ability to regenerate the spinal cord following complete transection, due to neural stem cell populations of ependymoglia. Previous work has shown that for ependymoglial-driven neural regeneration to occur, immune cells are a key requirement. However, in zebrafish the involvement of macrophages and the cytokine response during the process of spinal cord regeneration in post-larval stages remains poorly understood. In this study, I hypothesized that for functional recovery to occur, the pro-inflammatory response following SCI in zebrafish must be activated ahead of ependymoglial proliferation to initiate the regenerative process. To study this response, I developed a new juvenile model of SCI to then compare to the established adult model of SCI. By studying the spatiotemporal dynamics of immune cells post-SCI, I observed that overtime macrophages and microglia infiltrate into the injury site and contributed to cytokine release, correlating with a peak in proliferation of ependymoglia around the central canal. Interestingly, analysis of pro- and anti-inflammatory cytokines from RT-qPCR experiments demonstrated that pro-inflammatory cytokines are highly expressed shortly after injury, but are reduced to near control levels already by 3-days post-SCI. By contrast, anti-inflammatory cytokines appeared to play a minor role in the microenvironment post-SCI, remaining near control levels of expression. These findings propose that in order for successful spinal cord regeneration to occur in adult and juvenile zebrafish, a shorter pro-inflammatory response may be required to initiate ependymoglial proliferation in the spinal cord and restore functional repair.en_US
dc.description.noteMay 2022en_US
dc.identifier.urihttp://hdl.handle.net/1993/36398
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectzebrafishen_US
dc.subjectspinal cord injuryen_US
dc.subjectneuroregenerationen_US
dc.titleInvestigating the relationship between the immune response and ependymoglial activation during spinal cord regeneration in the adult and juvenile zebrafish modelen_US
dc.typemaster thesisen_US
project.funder.nameManitoba Medical Service Foundationen_US
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