Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway

Abstract

Abstract Resveratrol (RSV) attenuates early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study aimed to investigate whether the effects of RSV on SAH-induced EBI were mediated via the AMPK/SIRT1/autophagy pathway. A SAH rat model was established and oxyhemoglobin (Oxyhb)-induced primary cortical neurons were prepared to mimic SAH in vitro. The results showed that RSV significantly reduced microglia activation and the release of inflammatory cytokines, resulting in the alleviation of neurological behavior impairment, brain edema and neural apoptosis at 24 h post-SAH. However, RSV failed to ameliorate neurological deficits, brain edema and neural apoptosis when SAH injury lasted for 72 h. Additionally, at 24 h post-SAH, RSV-administered rats showed a significant increase in the LC3-II/I ratio and the phosphorylation state of AMPK and SIRT1 protein expression in brain tissues. Further in vitro studies revealed that RSV notably reduced the release of inflammatory cytokines and neural apoptosis in neurons at 24 post-Oxyhb, which was abolished by 3MA (an autophagy inhibitor) and Compound C (an AMPK inhibitor). Moreover, Compound C decreased LC3-II/I ratio and inhibited SIRT1 protein expression, whereas 3MA had no significant effects on AMPK/SIRT1-related proteins. In conclusion, the AMPK/SIRT1/autophagy pathway plays an important role in the alleviation of SAH-induced EBI by RSV.