Microglia reduce secondary neuronal cell death after brain injury in zebrafish

Centre for Neuroregeneration, Chancellor's Building, University of Edinburgh, EH16 4SB

Traumatic brain injury is a major cause of death and disability worldwide. While the primary insult cannot be prevented, a second wave of neuronal cell death lies within a therapeutic window of hours to days after the injury. Nonetheless, there are currently no pharmacological agents that consistently reduce secondary cell death after brain injury, indicating that the underlying mechanisms are incompletely understood. To study fundamental aspects of primary and secondary cell death in an accessible vertebrate model system, I have established a larval zebrafish model of mechanical brain injury. My data show that both primary and secondary cell death occur in wild type animals. Intriguingly, secondary cell death is greatly increased in a zebrafish mutant that lacks macrophages. This indicates that macrophages play a crucial tissue-protective function after brain injury in larval zebrafish. In further course of my research, I wilI aim to study the origin of the neuroprotective features of microglia in larval zebrafish: do microglia prevent secondary neuronal cell death by rapid phagocytosis of primary dead cells and thus clearance of debris and potential toxic factors, or do they exert neuroprotective functions via released molecules (or both)? For this I will manipulate microglial phagocytosis to study the contribution of debris removal to prevention of secondary cell death. My preliminary data show the upregulation of cytokines in microglia after the injury. I will employ cytokine release inhibitors to elucidate the function of these.

Funded by: University of Edinburgh

* entered into the PhD student poster competition