PUBLICATION
Rapid clearance of cellular debris by microglia limits secondary neuronal cell death after brain injury in vivo
- Authors
- Herzog, C., Pons Garcia, L., Keatinge, M., Greenald, D., Moritz, C., Peri, F., Herrgen, L.
- ID
- ZDB-PUB-190512-4
- Date
- 2019
- Source
- Development (Cambridge, England) 146(9): (Journal)
- Registered Authors
- Herrgen, Leah, Keatinge, Marcus, Peri, Francesca
- Keywords
- Brain injury, In vivo imaging, Microglia, Phagocytosis, Secondary cell death, Zebrafish
- MeSH Terms
-
- Animals
- Brain/cytology
- Brain/metabolism
- Brain Injuries/metabolism*
- Cell Death/physiology*
- Larva/cytology
- Larva/metabolism
- Macrophages/metabolism
- Microglia/metabolism*
- Neurons/cytology
- Neurons/metabolism
- Phagocytosis/physiology
- Zebrafish
- PubMed
- 31076485 Full text @ Development
Citation
Herzog, C., Pons Garcia, L., Keatinge, M., Greenald, D., Moritz, C., Peri, F., Herrgen, L. (2019) Rapid clearance of cellular debris by microglia limits secondary neuronal cell death after brain injury in vivo. Development (Cambridge, England). 146(9):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping