The Akt Pathway Is Involved in Rapid Ischemic Tolerance in Focal Ischemia in Rats

作     者：Gao, Xuwen Zhang, Hanfeng Steinberg, Gary Zhao, Heng 

作者机构：Stanford Univ Sch Med Dept Neurosurg Stanford CA 94305 USA Stanford Univ Sch Med Stanford Stroke Ctr Stanford CA 94305 USA 

出 版 物：《TRANSLATIONAL STROKE RESEARCH》 (转化脑卒中研究)

年 卷 期：2010年第1卷第3期

页      面：202-209页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：AHA [SDG 0730113N] NIH [1R21NS057750-01A2] NINDS [R01 NS27292, P01 NS37520] 

主　　题：Rapid preconditioning Ischemic tolerance Cerebral ischemia Focal ischemia Neuroprotection Akt 

摘      要：Although the protective mechanisms of delayed ischemic preconditioning have received extensive studies, few have addressed the mechanisms associated with rapid ischemic preconditioning. We investigated whether ischemic tolerance induced by rapid preconditioning is regulated by the Akt survival signaling pathway. Stroke was generated by permanent occlusion of the left distal middle cerebral artery plus 30 min or 1 h occlusion of the bilateral common carotid artery (CCA) in male rats. Rapid preconditioning performed 1 h before stroke onset reduced infarct size by 69% in rats with 30 min CCA occlusion, but by only 19% with 1 h occlusion. After control ischemia with 30 min CCA occlusion, Western blot showed that P-Akt was transiently increased while Akt kinase assay showed that Akt activity was decreased. Although preconditioning did not change P-Akt levels at 1 and 5 h compared with control ischemia, it attenuated reduction in Akt activity at 5 h in the penumbra. However, preconditioning did not change the levels of P-PDK1, P-PTEN, and P-GSK3 beta in the Akt pathway, all of which were decreased after stroke. At last, the PI3K kinase inhibitor, LY294002, completely reversed the protection from ischemic preconditioning. In conclusion, Akt contributes to the protection of rapid preconditioning against stroke.