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

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Abstract

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-GSK3β 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.

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Acknowledgements

The authors wish to thank Ms. Felicia F. Beppu for manuscript assistance and Ms. Elizabeth Hoyte for figure preparations. This study was supported by AHA grant SDG 0730113N (HZ) and NIH grant 1R21NS057750-01A2 (HZ), and NINDS grants R01 NS27292 (GKS) and P01 NS37520 (GKS).

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Authors and Affiliations

  1. Department of Neurosurgery, Stanford University School of Medicine, MSLS Bldg., P306, 1201 Welch Rd, Stanford, CA, 94305-5327, USA

    Xuwen Gao, Hanfeng Zhang, Gary Steinberg & Heng Zhao

  2. Stanford Stroke Center, Stanford University School of Medicine, MSLS Bldg., P306, 1201 Welch Rd, Stanford, CA, 94305-5327, USA

    Xuwen Gao, Hanfeng Zhang, Gary Steinberg & Heng Zhao

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  1. Xuwen Gao
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  2. Hanfeng Zhang
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  4. Heng Zhao
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Correspondence to Heng Zhao.

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Gao, X., Zhang, H., Steinberg, G. et al. The Akt Pathway Is Involved in Rapid Ischemic Tolerance in Focal Ischemia in Rats. Transl. Stroke Res. 1, 202–209 (2010). https://doi.org/10.1007/s12975-010-0017-5

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  • DOI: https://doi.org/10.1007/s12975-010-0017-5

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