Open AccessAKT / GSK 3β‐Dependent Autophagy Contributes to the Neuroprotection of Limb Remote Ischemic Postconditioning in the Transient Cerebral Ischemic Rat Model
Author(s) -
Qi ZhiFeng,
Luo YuMin,
Liu XiangRong,
Wang RongLiang,
Zhao HaiPing,
Yan Feng,
Song ZhaoJing,
Luo Mei,
Ji XunMing
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12016
Subject(s) - autophagy , protein kinase b , medicine , neuroprotection , gsk 3 , pi3k/akt/mtor pathway , ly294002 , phosphorylation , microbiology and biotechnology , pharmacology , chemistry , signal transduction , apoptosis , biology , biochemistry
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 .