Assessing the Cellular and Genetic Mechanisms of Regeneration in the Zebrafish Telencephalon in Response to Blunt-Force Traumatic Brain Injury

Traumatic brain injuries represent a large proportion of the global disease burden and can result in several short- and long-term deficits. Though humans possess adult neurogenesis, it is limited. Recently stem cell therapies aimed at transplantation of exogenous stem cells or stimulation of endogenous stem cells has been proposed to treat TBIs. Though promising, these studies show issues with survival, migration, and integration of progenitor cells. This highlights a lack of understanding of mechanisms necessary for regeneration. The zebrafish possess a robust regenerative capacity shown to respond to TBI in various parts of the central nervous system. This study proposes the use of a modified blunt-force TBI in the adult zebrafish telencephalon to examine cellular and molecular mechanisms of regeneration. This model induces a variety of TBI-related pathologies across different injury severities. I assess the mechanisms of cellular repair after severe TBI, which shows proliferation of radial glia, neural progenitors, and neuroblasts. Finally I assessed the genetic underpinnings of regeneration using a snRNA-Seq which suggested a role for PdgfrB in maintenance of the zebrafish NSCs. Perturbation of this pathway led to an increase in proliferating radial glia in the zebrafish telencephalon. Collectively, this study provides a foundation for future studies of injury-induced neuronal regeneration in the adult zebrafish and could be used to find druggable targets to increase neural repair in humans after TBI.