@article {Kondo4180, author = {Takeo Kondo and Andrew G. Reaume and Ting-Ting Huang and Elaine Carlson and Kensuke Murakami and Sylvia F. Chen and Eric K. Hoffman and Richard W. Scott and Charles J. Epstein and Pak H. Chan}, title = {Reduction of CuZn-Superoxide Dismutase Activity Exacerbates Neuronal Cell Injury and Edema Formation after Transient Focal Cerebral Ischemia}, volume = {17}, number = {11}, pages = {4180--4189}, year = {1997}, doi = {10.1523/JNEUROSCI.17-11-04180.1997}, publisher = {Society for Neuroscience}, 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{\textendash}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 situnick-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.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/17/11/4180}, eprint = {https://www.jneurosci.org/content/17/11/4180.full.pdf}, journal = {Journal of Neuroscience} }