Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia

Takeo Kondo, Andrew G. Reaume, Ting Ting Huang, Elaine Carlson, Kensuke Murakami, Sylvia F. Chen, Eric K. Hoffman, Richard W. Scott, Charles J. Epstein, Pak H. Chan

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392 Citations (Scopus)

Abstract

Apoptotic neuronal cell death has recently been associated with the development of infarction after cerebral ischemia. In a variety of studies, CuZn-superoxide dismutase (CuZn-SOD) has been shown to protect the brain from ischemic injury. A possible role for CuZn-SOD-related modulation of neuronal viability is suggested by the finding that CuZn-SOD inhibits apoptotic neuronal cell death in response to some forms of cellular damage. We evaluated this possibility in the model of transient focal cerebral ischemia in mice bearing a disruption of the CuZn-SOD gene (Sod1). Homozygous mutant (Sod1 -/-) mice had no detectable CuZn-SOD activity, and heterozygous mutants (Sod1 +/-) showed a 50% decrease compared with wild-type mice. Sod1 -/- mice showed a high level of blood-brain barrier disruption soon after 1 hr of middle cerebral artery occlusion and 100% mortality at 24 hr after ischemia. Sod1 +/- mice showed 30% mortality at 24 hr after ischemia, and neurological deficits were exacerbated compared with wild-type controls. The Sod1 +/- animals also had increased infarct volume and brain swelling, accompanied by increased apoptotic neuronal cell death as indicated by the in situ nick-end labeling technique to detect DNA fragmentation and morphological criteria. These results suggest that oxygen-free radicals, especially superoxide anions, are an important factor for the development of infarction by brain edema formation and apoptotic neuronal cell death after focal cerebral ischemia and reperfusion.

Original languageEnglish
Pages (from-to)4180-4189
Number of pages10
JournalJournal of Neuroscience
Volume17
Issue number11
DOIs
Publication statusPublished - 1997

Keywords

  • CuZn-superoxide dismutase
  • Evans blue extravasation
  • TUNEL
  • blood-brain barrier
  • focal cerebral ischemia
  • neuronal apoptosis
  • oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kondo, T., Reaume, A. G., Huang, T. T., Carlson, E., Murakami, K., Chen, S. F., Hoffman, E. K., Scott, R. W., Epstein, C. J., & Chan, P. H. (1997). Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. Journal of Neuroscience, 17(11), 4180-4189. https://doi.org/10.1523/jneurosci.17-11-04180.1997