title: Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus.
abstract: BACKGROUND
  Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R) injury. The P2X7 receptor (P2X7R) has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury.
  
  
  METHODS
  Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP) or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL). In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes.
  
  
  RESULTS
  The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg) and A-0438079 (3 μg), and a low dosage of OxATP (1 μg) significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus.
  
  
  CONCLUSIONS
  Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, 76 Qingchun Road, Hangzhou 310003, China.
authors.forename: Ketan
authors.initials: K
authors.lastname: Chu
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.forename: Jingye
authors.initials: J
authors.lastname: Wang
authors.forename: Guoping
authors.initials: G
authors.lastname: Peng
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Du
authors.forename: Marong
authors.initials: M
authors.lastname: Fang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.forename: Benyan
authors.initials: B
authors.lastname: Luo
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000502:physiology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D058920:Purinergic P2X Receptor Antagonists / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*
chemical_list: D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7