Translational Stroke Research

, Volume 5, Issue 6, pp 692–700 | Cite as

Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis

  • Xiangrong Liu
  • Shangfeng Zhao
  • Fang Liu
  • Jun Kang
  • Ao Xiao
  • Fang Li
  • Chencheng Zhang
  • Feng Yan
  • Haiping Zhao
  • Mei Luo
  • Yumin Luo
  • Xunming Ji
Original Article
First Online:
Received:
Revised:
Accepted:

Abstract

Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2. Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis.

Keywords

Cerebral ischemia CHOP ER stress Apoptosis Ischemic postconditioning Neuroprotection 
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Notes

Acknowledgments

This work was supported by the Natural Science Foundation of China (Grant nos. 81000504, 81171241, 81271462) and Beijing Natural Science Foundation (Grant nos. 7111003, 7132112).

Conflict of Interest

Xiangrong Liu, Shangfeng Zhao, Fang Liu, Jun Kang, Ao Xiao, Fang Li, Chencheng Zhang, Feng Yan, Haiping Zhao, Mei Luo, Yumin Luo, and Xunming Ji declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiangrong Liu
    • 1
    • 2
    • 5
  • Shangfeng Zhao
    • 3
  • Fang Liu
    • 1
    • 2
    • 5
  • Jun Kang
    • 3
  • Ao Xiao
    • 1
  • Fang Li
    • 1
  • Chencheng Zhang
    • 1
    • 2
    • 5
  • Feng Yan
    • 1
    • 2
    • 5
  • Haiping Zhao
    • 1
    • 2
    • 5
  • Mei Luo
    • 1
  • Yumin Luo
    • 1
    • 2
    • 5
  • Xunming Ji
    • 1
    • 2
    • 4
  1. 1.Cerebrovascular Diseases Research InstituteXuanwu Hospital of Capital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Key Laboratory of Neurodegenerative Diseases, Ministry of EducationBeijingPeople’s Republic of China
  3. 3.Department of NeurosurgeryBeijing Tongren Hospital, Capital Medical UniversityBeijingPeople’s Republic of China
  4. 4.Department of NeurosurgeryXuanwu Hospital of Capital Medical UniversityBeijingPeople’s Republic of China
  5. 5.Beijing Key Laboratory of Translational Medicine for Cerebrovascular DiseasesBeijingChina

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