Implication of cyclooxygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia.
Global ischemia promotes neurogenesis in the dentate gyrus of the adult mouse hippocampus. Cyclooxygenase (COX)-2, the principal isoenzyme in the brain, modulates inflammation, glutamate-mediated cytotoxicity, and synaptic plasticity. We demonstrated that delayed treatment with different classes of COX inhibitor significantly blunted enhancement of dentate gyrus proliferation of neural progenitor cells after ischemia. COX-2 immunoreactivity was observed in both neurons and astrocytes in the dentate gyrus, but not in neural progenitor cells in the subgranular zone. Moreover, in the postischemic dentate gyrus of heterozygous and homozygous COX-2 knockout mice, proliferating bromodeoxyuridine-positive cells were significantly fewer than in wild-type littermates. These results demonstrate that COX-2 is an important modulator in enhancement of proliferation of neural progenitor cells after ischemia.
Sasaki
Tsutomu
T
Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. sasaki@medone.med.osaka-u.ac.jp
Kitagawa
Kazuo
K
Sugiura
Shiro
S
Omura-Matsuoka
Emi
E
Tanaka
Shigeru
S
Yagita
Yoshiki
Y
Okano
Hideyuki
H
Matsumoto
Masayasu
M
Hori
Masatsugu
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin