AKT / GSK 3β‐Dependent Autophagy Contributes to the Neuroprotection of Limb Remote Ischemic Postconditioning in the Transient Cerebral Ischemic Rat Model

Summary Background Limb remote ischemic postconditioning ( RIP ost C ) has been recognized as an applicable strategy in protecting against cerebral ischemic injury. However, the time window for application of limb RIP ost C and the mechanisms behind RIP ost C are still unclear. Aims In this study, we investigated the protective efficacy and the role of autophagy in limb RIP ost C using a transient middle cerebral artery occlusion rat model. Results Limb RIP ost C applied in the early phase of reperfusion reduced infarct size and improved neurological function. Autophagy levels in penumbral tissues were elevated in neurons of limb RIP ost C rats, with an increase in the phosphorylation of AKT and glycogen synthase kinase 3β ( GSK 3β). Blocking the AKT / GSK 3β pathway via the AKT inhibitor LY 294002 prior to limb RIP ost C suppressed the RIP ost C ‐induced autophagy and resulted in the activation of caspase‐3 in RIP ost C rats, suggesting a critical role for AKT / GSK 3β‐dependent autophagy in reducing cell death after cerebral ischemia. Conclusions These results aid optimization of the time window for RIP ost C use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIP ost C .