title: Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia.
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.
authors.affiliation: 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.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Guo
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Cheng
authors.initials: C
authors.lastname: He
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Burnstock
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yuan
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Xiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7