Endoplasmic Reticulum Stress Is Associated With Neuroprotection Against Apoptosis Via Autophagy Activation In A Rat Model Of Subarachnoid Hemorrhage

Endoplasmic reticulum (ER) stress might play an important role in a range of neurological diseases and its role in subarachnoid hemorrhage(SAH) remains unclear. In the present study, the potential role of endoplasmic reticulum stress in early brain injury following SAH was explored.Methods:The84rats were intraperitoneally pretreated with the ER stress inducer tunicamycin (Tm) or with the inhibitor tauroursodeoxycholic acid (TUDCA) or autophagy inhibitor3-methyladenine (3-MA) before SAH onset. At24hours, rats were neurologically evaluated, and their brains were extracted for molecular biological and histologicalstudies.Results:ER stress was upregulated in rats after SAH. Enhanced ER stress significantly improved neurological deficits, attenuated the expression of pro-apoptotic molecules of caspase-3and reduced the number of TUNEL-positive cells. In contrast, TUDCA aggravated neurological deficits and apoptotic cell death. The levels of the autophagic protein Beclin1and the ratio of LC3-II to LC3-I were both increased by Tm infusion and reduced by TUDCA. The inhibition of autophagic activity with3-MA reduced Tm-induced anti-apoptotic effects.Conclusion:Our study indicates that ER stress alleviates early brain injury following SAH via inhibiting apoptosis. This neuroprotective effect is likely associated with autophagy activation...