Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion

Pak H. Chan, Makoto Kawase, Kensuke Murakami, Sylvia F. Chen, Yibing Li, Bernard Calagui, Liza Reola, Elaine Carlson, Charles J. Epstein

    研究成果: Article査読

    283 被引用数 (Scopus)

    抄録

    Transient global cerebral ischemia resulting from cardiac arrest is known to cause selective death in vulnerable neurons, including hippocampal CA1 pyramidal neurons. It is postulated that oxygen radicals, superoxide in particular, are involved in cell death processes. To test this hypothesis, we first used in situ imaging of superoxide radical distribution by hydroethidine oxidation in vulnerable neurons. We then generated SOD1 transgenic (Tg) rats with a five-fold increase in copper zinc superoxide dismutase activity. The Tg rats and their non-Tg wild-type littermates were subjected to 10 min of global ischemia followed by 1 and 3 d of reperfusion. Neuronal damage, as assessed by cresyl violet staining and DNA fragmentation analysis, was significantly reduced in the hippocampal CA1 region, cortex, striatum, and thalamus in SOD1 Tg rats at 3 d, as compared with the non-Tg littermates. There were no changes in the hippocampal CA3 subregion and dentate gyrus, resistant areas in both SOD1 Tg and non-Tg rats. Quantitative analysis of the damaged CA1 subregion showed marked neuroprotection against transient global cerebral ischemia in SOD1 Tg rats. These results suggest that superoxide radicals play a role in the delayed ischemic death of hippocampal CA1 neurons. Our data also indicate that SOD1 Tg rats are useful tools for studying the role of oxygen radicals in the pathogenesis of neuronal death after transient global cerebral ischemia.

    本文言語English
    ページ(範囲)8292-8299
    ページ数8
    ジャーナルJournal of Neuroscience
    18
    20
    DOI
    出版ステータスPublished - 1998 10 15

    ASJC Scopus subject areas

    • Neuroscience(all)

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