Microglia/macrophages require vitamin D signaling to restrain neuroinflammation and brain injury in a murine ischemic stroke model.

ABSTRACT: Vitamin D deficiency is associated with worse clinical outcomes after ischemic stroke; nevertheless, the pathophysiological mechanisms remain largely unexplored. In this study, we characterized the molecular mechanisms of how vitamin D signaling modulated stroke progression in male mouse ischemia-reperfusion stroke models. We found that vitamin D receptor (VDR) exhibited a predominant upregulation in peri-infarct microglia/macrophages following cerebral ischemia. Conditional Vdr inactivation in microglia/macrophages markedly augmented infarct volumes and neurological deficits. VDR-deficient microglia/macrophages exhibited a more primed proinflammatory phenotype with substantial secretion of TNF-α and IFN-γ. These inflammatory cytokines further enhanced CXCL10 release from endothelial cells

SUBMITTER: Cui P 

PROVIDER: S-EPMC9993716 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature