Sodium selenite mitigates hyperglycemia-aggravated cerebral ischemia/reperfusion injury via the p53/PUMA apoptotic pathway

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury, a severe ischemic stroke complication with few treatments. Selenium exerts neuroprotective effects, yet its molecular mechanisms in this injury remain unclear. This study explored whether sodium selenite alleviates the injury via regulating the p53/PUMA apoptotic pathway and the role of selenoprotein H (SelH). In vivo, Sprague-Dawley rats (including PUMA-knockdown models) were subjected to middle cerebral artery occlusion/reperfusion; in vitro, HT22 cells (PUMA-knockdown/SelH-overexpressing) were treated with high glucose and oxygen-glucose deprivation/reoxygenation. Results showed hyperglycemia exacerbated neurological deficits, infarct volume, neuronal apoptosis and mitochondrial damage in vivo, and induced ROS overproduction, mitochondrial dysfunction and apoptosis in vitro. Sodium selenite reversed these injuries, downregulated p53/PUMA pathway-related proteins, upregulated the bcl-2/Bax ratio, and elevated SelH expression. PUMA knockdown enhanced its neuroprotection, while SelH overexpression attenuated cell damage by inhibiting the p53/PUMA pathway (not direct oxidative stress reduction). Thus, sodium selenite mitigates hyperglycemia-aggravated cerebral I/R injury through the SelH-p53/PUMA pathway, providing novel therapeutic targets for diabetic stroke.