Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes.

ABSTRACT: Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) contributes to long-term tissue damage and poor functional outcomes. However, the mechanisms contributing to exacerbated inflammatory responses after brain injury remain poorly understood. Our previous work showed that macroautophagy/autophagy flux is inhibited in neurons following TBI in mice and contributes to neuronal cell death. In the present study, we demonstrate that autophagy is also inhibited in activated microglia and infiltrating macrophages, and that this potentiates injury-induced neuroinflammatory responses. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 led to overall increase in neuroinflammation after TBI. In particular, we observed excessive activation of

SUBMITTER: Hegdekar N 

PROVIDER: S-EPMC10283445 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature