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

    Research output: Contribution to journalArticlepeer-review

    282 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)8292-8299
    Number of pages8
    JournalJournal of Neuroscience
    Volume18
    Issue number20
    DOIs
    Publication statusPublished - 1998 Oct 15

    Keywords

    • DNA fragmentation
    • Delayed neuronal degeneration
    • Superoxide dismutase
    • Superoxide radicals
    • Transgenic rat
    • Transient global cerebral ischemia

    ASJC Scopus subject areas

    • Neuroscience(all)

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