title: Prostaglandin E2 produced by late induced COX-2 stimulates hippocampal neuron loss after seizure in the CA3 region.
abstract: Injection of kainic acid (KA) into the brain causes severe seizures with hippocampal neuron loss. KA has been shown to immediately induce cyclooxygenase-2 (COX-2) expression in hippocampal neurons, indicating that neuronal COX-2 might be involved in neuronal death. In this study, however, we reveal that the delayed COX-2 induction in non-neuronal cells after KA injection plays an important role in hippocampal neuron loss rather than early COX-2 expression in neurons. We find that KA microinjection into the hemilateral hippocampus shows a later induction of COX-2 expression in non-neuronal cells, such as endothelial cells and astrocytes. In the KA-injected side, PGE2 concentration gradually increases and peaks at 24 h after injection, when non-neuronal COX-2 expression also peaks. When this delayed PGE2 elevation is prevented by selective COX-2 inhibitor NS398, it can block hippocampal cell death. Moreover, COX-2 knockout mice are also resistant to neuronal death after KA treatment. These findings indicate that delayed PGE2 production by non-neuronal COX-2 may facilitate neuronal death after seizure. Inhibition of COX-2 to an extent similar to PGE2 elevation after onset of seizure may be useful to prevent neuronal death.
authors.affiliation: Department of Neuropharmacology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan. takakot@tmin.ac.jp
authors.forename: Takako
authors.initials: T
authors.lastname: Takemiya
authors.forename: Michiyo
authors.initials: M
authors.lastname: Maehara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumura
authors.forename: Shin
authors.initials: S
authors.lastname: Yasuda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sugiura
authors.forename: Kanato
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009578:Nitrobenzenes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D018690:Excitatory Amino Acid Agonists; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007608:Kainic Acid