BRG1 alleviates microglial activation by promoting the KEAP1-NRF2/HO-1 signaling pathway and minimizing oxidative damage in cerebral ischemia-reperfusion.

BRG1 is a key factor in the process of apoptosis and oxidative damage; however, its role in the pathophysiology of ischemic stroke is unclear. Here, we discovered that during middle cerebral artery occlusion (MCAO) reperfusion in mice, microglia were significantly activated in the cerebral cortex of the infarct area, and BRG1 expression was increased in the mouse MCAO/R model, peaking at 4 days. In microglia subjected to OGD/R, BRG1 expression increased and peaked at 12 h after reoxygenation. After ischemic stroke, in vitro changing the expression of BRG1 expression levels greatly altered the activation of microglia and the production of antioxidant and pro-oxidant proteins. Knocking down BRG1 expression levels in vitro increased the inflammatory response, promoted microglial activation, and decreased the expression of the NRF2/HO-1 signaling pathway after ischemic stroke. In contrast, overexpression of BRG1 dramatically reduced the expression of NRF2/HO-1 signaling pathway and microglial activation. Our research reveals that BRG1 reduces postischemic oxidative damage via the KEAP1-NRF2/HO-1 signaling pathway, protecting against brain ischemia/reperfusion injury. Using BRG1 as a pharmaceutical target to inhibit inflammatory responses to reduce oxidative damage may be a unique way to explore techniques for the treatment of ischemic stroke and other cerebrovascular illnesses.