Excitotoxicity-induced immediate surge in hippocampal prostanoid production has latent effects that promote chronic progressive neuronal death

Keisuke Yoshikawa, Yoshihiro Kita, Ayako Furukawa, Noriko Kawamura, Sanae Hasegawa-Ishii, Yoichi Chiba, Shiro Takei, Kei Maruyama, Takao Shimizu, Atsuyoshi Shimada

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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.

Original languageEnglish (US)
Pages (from-to)373-381
Number of pages9
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume88
Issue number5
DOIs
StatePublished - May 1 2013

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

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    Yoshikawa, K., Kita, Y., Furukawa, A., Kawamura, N., Hasegawa-Ishii, S., Chiba, Y., Takei, S., Maruyama, K., Shimizu, T., & Shimada, A. (2013). Excitotoxicity-induced immediate surge in hippocampal prostanoid production has latent effects that promote chronic progressive neuronal death. Prostaglandins Leukotrienes and Essential Fatty Acids, 88(5), 373-381. https://doi.org/10.1016/j.plefa.2013.02.007