title: Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.
abstract: Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce susceptibility to focal ischemic injury and N-methyl-d-aspartate-mediated neurotoxicity. The purpose of this study was to examine the effects of COX-2 deficiency on neuronal vulnerability after transient forebrain ischemia. Marked upregulation of COX-2 immunostaining in neurons was observed at the early stage and prominent COX-2 staining persisted in the CA1 medial sector and CA2 sector over 3 days after ischemia. The immunohistologic pattern of COX-2 staining in these sectors gradually condensed to a perinuclear location. The degree of hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice was less than that in wild-type mice, coincident with attenuation of DNA fragmentation in the hippocampus. Also, treatment with a selective COX-2 inhibitor, nimesulide, after ischemia decreased hippocampal neuronal damages. These results of genetic disruption and chemical inhibition of cyclooxygenase-2 show that inhibition of COX-2 ameliorates selective neuronal death after transient forebrain ischemia in mice.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. sasaki@medone.med.osaka-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Kanato
authors.initials: K
authors.lastname: Yamagata
authors.forename: Takako
authors.initials: T
authors.lastname: Takemiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.forename: Emi
authors.initials: E
authors.lastname: Omura-Matsuoka
authors.forename: Shiro
authors.initials: S
authors.lastname: Sugiura
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000473:pathology*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide