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Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia

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Abstract

Transient global ischemia (which closely resembles clinical situations such as cardiac arrest, near drowning or severe systemic hypotension during surgical procedures), often induces delayed neuronal death in the brain, especially in the hippocampal CA1 region. The mechanism of ischemia/reperfusion (I/R) injury is not fully understood. In this study, we have shown that the P2X7 receptor antagonist, BBG, reduced delayed neuronal death in the hippocampal CA1 region after I/R injury; P2X7 receptor expression levels increased before delayed neuronal death after I/R injury; inhibition of the P2X7 receptor reduced I/R-induced microglial microvesicle-like components, IL-1β expression, P38 phosphorylation, and glial activation in hippocampal CA1 region after I/R injury. These results indicate that antagonism of the P2X7 receptor and signaling pathways of microglial MV shedding, such as src-protein tyrosine kinase, P38 MAP kinase and A-SMase, might be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.

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Acknowledgments

The authors thank Dr. Gillian E. Knight for her excellent editorial assistance. This work was supported by 973 Program (2011CB504401 to Z. Xiang) and the National Natural Science Foundation of the People’s Republic of China (30970918 to Z. Xiang).

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Authors and Affiliations

  1. Department of Neurobiology, MOE Key Laboratory of Molecular Neurobiology, Ministry of Education, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Qiang Yu, Xiaofeng Liu, Cheng He & Zhenghua Xiang

  2. Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Zhili Guo

  3. Department of Anesthesiology, Neuroscience Research Centre, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Qing Ouyang & Hongbin Yuan

  4. Autonomic Neuroscience Centre, University College Medical School, Rowland Hill Street, London NW3 2PF and Department of Pharmacology, Melbourne University, Parkville, Australia

    Geoffrey Burnstock

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  1. Qiang Yu
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Correspondence to Hongbin Yuan or Zhenghua Xiang.

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Q Yu, Z Guo and X Liu contributed equally to this work.

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Yu, Q., Guo, Z., Liu, X. et al. Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia. Purinergic Signalling 9, 663–675 (2013). https://doi.org/10.1007/s11302-013-9379-y

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