Sodium selenite attenuates hyperglycemia-exacerbated cerebral ischemia/reperfusion injury by inhibiting the Fas/FasL/PUMA apoptotic pathway.

Hyperglycemia exacerbates cerebral ischemia/reperfusion (I/R) injury, apoptosis pathways playing a key role. Sodium selenite (SE) exhibits neuroprotective effects, however, whether the Fas/FasL/PUMA pathway is involved in this neuroprotective effects remains unclear. For help to make this clear, hyperglycemic-aggravated cerebral I/R models (SD rats) and in vitro high-glucose oxygen deprivation/reoxygenation (OD/R) models (HT22 cells) were applied in this study. This study showed that the cerebral infarct volume and neuronal damages in the hyperglycemic I/R rat indeed were alleviated by the selenite treatment. And the lost neurological functions were improved by selenite treatment also. In the HT22 cells, the SE treatment enhanced viability and reduced reactive oxygen species (ROS) accumulation. Mechanistically, this study showed that the SE treatment downregulated the expressions of Fas, FasL, p-NF-κB, PUMA, Cleaved Caspase-3, and Cytochrome c, while increased the Bcl-2/Bax expression ratio. The SE's anti-apoptotic effects were potentiated by PUMA knockdown or autophagy inhibitor 3-MA co-treatment. These findings confirm that SE alleviates hyperglycemia-exacerbated cerebral I/R injury by inhibiting the Fas/FasL/PUMA apoptotic pathway, providing a therapeutic strategy for hyperglycemia ischemic stroke. CONCLUSION: Sodium selenite alleviates hyperglycemia-exacerbated cerebral I/R injury by modulating the Fas/FasL/PUMA signaling pathway. SIGNIFICANCE STATEMENT: The finding that sodium selenite alleviates hyperglycemia - exacerbated cerebral I/R injury by modulating the Fas/FasL/PUMA signaling pathway advances knowledge in neuroscience by revealing a novel mechanism through which a compound can mitigate the harmful effects of hyperglycemia on cerebral I/R injury, and it deepens our understanding of how apoptotic pathways in the nervous system can be regulated to protect against such injuries.