title: AKT/GSK3β-dependent autophagy contributes to the neuroprotection of limb remote ischemic postconditioning in the transient cerebral ischemic rat model.
abstract: BACKGROUND
  Limb remote ischemic postconditioning (RIPostC) has been recognized as an applicable strategy in protecting against cerebral ischemic injury. However, the time window for application of limb RIPostC and the mechanisms behind RIPostC are still unclear.
  
  
  OBJECTIVE
  In this study, we investigated the protective efficacy and the role of autophagy in limb RIPostC using a transient middle cerebral artery occlusion rat model.
  
  
  RESULTS
  Limb RIPostC 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 RIPostC rats, with an increase in the phosphorylation of AKT and glycogen synthase kinase 3β (GSK3β). Blocking the AKT/GSK3β pathway via the AKT inhibitor LY294002 prior to limb RIPostC suppressed the RIPostC-induced autophagy and resulted in the activation of caspase-3 in RIPostC rats, suggesting a critical role for AKT/GSK3β-dependent autophagy in reducing cell death after cerebral ischemia.
  
  
  CONCLUSIONS
  These results aid optimization of the time window for RIPostC use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIPostC.
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu hospital of Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Qi
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Luo
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Liu
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Wang
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Zhao-Jing
authors.initials: ZJ
authors.lastname: Song
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.forename: Xun-Ming
authors.initials: XM
authors.lastname: Ji
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D020244:Infarction, Middle Cerebral Artery; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3