title: Deficiency of PAR-2 gene increases acute focal ischemic brain injury.
abstract: The expression profile of the protease-activated receptor-2 (PAR-2) and effects of PAR-2 gene knockout (PAR-2 KO) on the infarct size were investigated after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice in relation to phosphorylated extracellular signal-regulated kinase (p-ERK) and astrocyte activation. PAR-2 was normally distributed mainly in neurons of the central nervous system (CNS), and strongly upregulated at 8-24 hours after tMCAO. Deficiency of PAR-2 gene significantly increased the infarct volume and the number of TUNEL-positive cells at 24 hours of reperfusion. The strong neuronal expression of p-ERK was induced at 5 minutes as a peak after reperfusion in wild-type mice, but the signal change was significantly reduced in PAR-2 KO mice. Astroglial activation was also greatly inhibited at 24 hours after tMCAO in PAR-2 KO mice. These results show that the deficiency of PAR-2 gene increases the acute ischemic cerebral injury associating with suppression of neuronal ERK activation and reactive astroglial activation.
authors.affiliation: Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawagoe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takizawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagata
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Mikio
authors.initials: M
authors.lastname: Syoji
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology; D044464:Receptor, PAR-2 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D044464:Receptor, PAR-2; D048049:Extracellular Signal-Regulated MAP Kinases