Roles of autophagy and endoplasmic reticulum stress in intracerebral hemorrhage-induced secondary brain injury inrats.

Abstract

This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. Autophagy and ER stress were enhanced in the week after ICH. At 6hours after ICH, autophagy was excessive, while the autophagic flux was damaged at 72hours and return to be intact at 7days after ICH. At 6hours after ICH, ER stress induction by TM could enhance autophagy and lead to caspase 12-mediated apoptosis and neuronal degeneration, which was further aggravated by autophagy induction. At 7days after ICH, ER stress inhibition by TUDCA still could suppress ICH-induced SBI. And, the effects of TUDCA were enhanced by autophagy induction. At 6hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7days after ICH, autophagy could enhance the protection of ER stress inhibitor possibly via clearing up the cell rubbish generated due to the early-stage damaged autophagic flux.