Journal
DEVELOPMENT
Volume 146, Issue 9, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.174698
Keywords
Brain injury; Secondary cell death; Microglia; Phagocytosis; In vivo imaging; Zebrafish
Categories
Funding
- University of Edinburgh Chancellor's Fellowship
- Wellcome Trust/The University of Edinburgh Institutional Strategic Support Fund
- Carnegie Trust for the Universities of Scotland Research Incentive Grant [70457]
- Rosetrees Trust/Stoneygate Trust Seedcorn Award [M602]
- Wellcome Trust Seed Award in Science [207701/Z/17/Z]
- Wellcome Trust [207701/Z/17/Z] Funding Source: Wellcome Trust
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Moderate or severe traumatic brain injury (TBI) causes widespread neuronal cell death. Microglia, the resident macrophages of the brain, react to injury by migrating to the lesion site, where they phagocytose cellular debris. Microglial phagocytosis can have both beneficial (e.g. debris clearance) and detrimental (e.g. respiratory burst, phagoptosis) consequences. Hence, whether the overall effect of microglial phagocytosis after brain injury in vivo is neuroprotective or neurotoxic is not known. Here, we establish a system with which to carry out dynamic real-time analyses of the mechanisms regulating cell death after brain injury in vivo. We show that mechanical injury to the larval zebrafish brain induces distinct phases of primary and secondary cell death. Excitotoxicity contributes to secondary cell death in zebrafish, reflecting findings from mammals. Microglia arrive at the lesion site within minutes of injury, where they rapidly engulf dead cells. Importantly, the rate of secondary cell death is increased when the rapid removal of cellular debris by microglia is reduced pharmacologically or genetically. In summary, our results provide evidence that microglial debris clearance is neuroprotective after brain injury in vivo.
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