title: Excitotoxicity-induced immediate surge in hippocampal prostanoid production has latent effects that promote chronic progressive neuronal death.
abstract: Excitotoxicity is involved in neurodegenerative conditions. We investigated the pathological significance of a surge in prostaglandin production immediately after kainic acid (KA) administration [initial phase], followed by a sustained moderate elevation in prostaglandin level [late phase] in the hippocampus of juvenile rats. Numerous pyknotic hippocampal neurons were observed 72 h after KA treatment; this number remained elevated on days 10 and 30. Gross hippocampal atrophy was observed on days 10 and 30. Pre-treatment with indomethacin ameliorated neuronal death on days 10 and 30, and prevented hippocampal atrophy on day 30. Microglial response was moderated by the indomethacin pre-treatment. Blockade of only late-phase prostaglandin production by post-treatment with indomethacin ameliorated neuronal death on day 30. These findings suggest a role for initial-phase prostaglandin production in chronic progressive neuronal death, which is exacerbated by late-phase prostaglandin production. Blockade of prostaglandin production has therapeutic implications in preventing long-term neurological sequelae following excitotoxic brain damage.
authors.affiliation: Division of Neuropathology, Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya, Kasugai, Aichi 480-0392, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kita
authors.forename: Ayako
authors.initials: A
authors.lastname: Furukawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Kawamura
authors.forename: Sanae
authors.initials: S
authors.lastname: Hasegawa-Ishii
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Chiba
authors.forename: Shiro
authors.initials: S
authors.lastname: Takei
authors.forename: Kei
authors.initials: K
authors.lastname: Maruyama
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
mesh_terms: D000818:Animals; D016923:Cell Death; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011453:Prostaglandins; D007608:Kainic Acid