Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1

Hidekatsu Mizushima, Cheng J I Zhou, Kenji Dohi, Reiko Horai, Masahide Asano, Yoichiro Iwakura, Takahiro Hirabayashi, Satoru Arata, Shigeo Nakajo, Atsushi Takaki, Hirokazu Ohtaki, Seiji Shioda

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Abstract

The cytokine interleukin-1 (IL-1) has been implicated in ischemic brain damage, because the IL-1 receptor antagonist markedly inhibits experimentally induced neuronal loss. However, to date, no studies have demonstrated the involvement of endogenous IL-1α and IL-1β in neurodegeneration. We report here, for the first time, that mice lacking IL-1α/β (double knockout) exhibit markedly reduced neuronal loss and apoptotic cell death when exposed to transient cardiac arrest. Furthermore, we show that, despite the reduced neuronal loss, phosphorylation of JNK/SAPK (c-Jun NH2-terminal protein kinase/stress activated protein kinase) and p38 enzymes remain elevated in IL-1 knockout mice. In contrast, the inducible nitric oxide (iNOS) immunoreactivity after global ischemia was reduced in IL-1 knockout mice as compared with wild-type mice. The levels of nitrite (NO2-) and nitrate (NO3-) in the hippocampus of wild-type mice were increased with time after ischemia-reperfusion, whereas the increase was significantly inhibited in IL-1 knockout mice. These observations strongly suggest that endogenous IL-1 contributes to ischemic brain damage, and this influence may act through the release of nitric oxide by iNOS.

Original languageEnglish
Pages (from-to)203-216
Number of pages14
JournalJournal of Comparative Neurology
Volume448
Issue number2
DOIs
Publication statusPublished - 2002

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Mizushima, H., Zhou, C. J. I., Dohi, K., Horai, R., Asano, M., Iwakura, Y., ... Shioda, S. (2002). Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1. Journal of Comparative Neurology, 448(2), 203-216. https://doi.org/10.1002/cne.10262