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

Thumbnail Image
Trzuskot, Lidia
Journal Title
Journal ISSN
Volume Title
Spinal 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.
zebrafish, spinal cord injury, neuroregeneration