Catestatin attenuates cerebral ischemia/reperfusion injury and suppresses endoplasmic reticulum stress.

Ischemic stroke is one of the leading causes of death worldwide. Catestatin (CST), as a pleiotropic hormone, displays an anti-apoptotic effect, in addition to its known roles in cardiovascular regulation. However, the role of CST in ischemic stroke remains unclear. In this study, we investigated the temporal changes of CST levels in the cortex and serum of middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Intracerebroventricular administration of CST significantly alleviated neurological deficits, reduced cerebral infarct volume, cerebral edema, and pathological damage, while attenuating neuronal apoptosis and modulating apoptosis-related proteins. Notably, CST suppressed endoplasmic reticulum stress (ERS) by inhibiting the PERK pathway. Furthermore, in vitro experiments using the oxygen-glucose deprivation/reperfusion (OGD/R) model of PC12 cells demonstrated that CST similarly inhibited apoptosis, as evidenced by flow cytometry and consistent changes in apoptosis-related proteins. These findings collectively demonstrate that CST exerts neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI), with these effects potentially mediated through inhibition of ERS via the PERK signaling pathway.