Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.
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.
Sasaki
Tsutomu
T
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. sasaki@medone.med.osaka-u.ac.jp
Kitagawa
Kazuo
K
Yamagata
Kanato
K
Takemiya
Takako
T
Tanaka
Shigeru
S
Omura-Matsuoka
Emi
E
Sugiura
Shiro
S
Matsumoto
Masayasu
M
Hori
Masatsugu
M
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
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide