| First Author | Cui P | Year | 2023 |
| Journal | J Neuroinflammation | Volume | 20 |
| Issue | 1 | Pages | 63 |
| PubMed ID | 36890539 | Mgi Jnum | J:338485 |
| Mgi Id | MGI:7443629 | Doi | 10.1186/s12974-023-02705-0 |
| Citation | Cui P, et al. (2023) Microglia/macrophages require vitamin D signaling to restrain neuroinflammation and brain injury in a murine ischemic stroke model. J Neuroinflammation 20(1):63 |
| abstractText | 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-alpha and IFN-gamma. These inflammatory cytokines further enhanced CXCL10 release from endothelial cells and blood-brain barrier disruption, and ultimately infiltration of peripheral T lymphocytes. Notably, blocking TNF-alpha and IFN-gamma significantly ameliorated stroke phenotypes in Vdr conditional knockout mice. Collectively, VDR signaling in microglia/macrophages plays a crucial role in restraining ischemia-elicited neuroinflammation and stroke progression. Our findings delineate a novel mechanism underlying the association between vitamin D deficiency and poor stroke outcomes, and underline the significance of maintaining a functional vitamin D signaling in the management of acute ischemic stroke. |
