Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain

Yoichi Kondo, Masato Asanuma, Sakiko Nishibayashi, Emi Iwata, Norio Ogawa

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

We previously reported that iron deposition was seen in the cerebral cortex and hippocampal CA1 area late after transient forebrain ischemia generated by four-vessel occlusion in rats. Iron deposition in the hippocampal CA1 area was coupled with delayed pyramidal cell death, while that in the cerebral cortex was not accompanied by neuronal death or atrophy until 6 months after ischemia. Iron is involved in the formation of free radicals, thus contributing to lipid peroxidation. To elucidate whether this iron has deleterious effects on neurons, we investigated changes in the levels of lipid peroxidation and resulting neuronal damage in this ischemia model. The level of malondialdehyde plus 4-hydroxynonenal as major decomposition products of lipid peroxidation, monitored for 6 months beginning just after 30 min of transient forebrain ischemia, was significantly increased in the cerebral cortex at 6 months, and in the striatum from 1 week to 6 months compared to that in sham-operated controls. Histological changes were also examined up to 1 year after reperfusion by immunohistochemical methods. In contrast with the hippocampus and striatum, the cerebral cortex did not develop severe neuronal cell death and atrophy until 1 year after the ischemic insult. We showed that lipid peroxidation took place not only immediately after ischemia-reperfusion but also late after the ischemic insult in regions where iron was deposited, and we showed that neuronal cell death in the cerebral cortex appeared extremely late, suggesting that iron-mediated lipid peroxidation may be of importance in some slowly progressive forms of neurodegeneration.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalBrain Research
Volume772
Issue number1-2
DOIs
Publication statusPublished - Oct 24 1997

Keywords

  • Cerebral ischemia
  • Cortex
  • Iron
  • Lipid peroxidation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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