Abstract
Objectives:
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.
Methods:
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.
Results:
Autophagy and ER stress were enhanced in the week after ICH. At 6 hours after ICH, autophagy was excessive, while the autophagic flux was damaged at 72 hours and return to be intact at 7 days after ICH. At 6 hours 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 7 days after ICH, ER stress inhibition by TUDCA still could suppress ICH-induced SBI. And, the effects of TUDCA were enhanced by autophagy induction.
Conclusions:
At 6 hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7 days 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.
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