Reduction of CuZn-Superoxide Dismutase Activity Exacerbates Neuronal Cell Injury and Edema Formation after Transient Focal Cerebral Ischemia

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 v...

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Veröffentlicht in:The Journal of neuroscience 1997-06, Vol.17 (11), p.4180-4189
Hauptverfasser: Kondo, Takeo, Reaume, Andrew G, Huang, Ting-Ting, Carlson, Elaine, Murakami, Kensuke, Chen, Sylvia F, Hoffman, Eric K, Scott, Richard W, Epstein, Charles J, Chan, Pak H
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container_end_page 4189
container_issue 11
container_start_page 4180
container_title The Journal of neuroscience
container_volume 17
creator Kondo, Takeo
Reaume, Andrew G
Huang, Ting-Ting
Carlson, Elaine
Murakami, Kensuke
Chen, Sylvia F
Hoffman, Eric K
Scott, Richard W
Epstein, Charles J
Chan, Pak H
description 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.
doi_str_mv 10.1523/jneurosci.17-11-04180.1997
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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. 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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. 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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.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>9151735</pmid><doi>10.1523/jneurosci.17-11-04180.1997</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Apoptosis - physiology
Biotin
Blood-Brain Barrier - physiology
Cell Death - physiology
Cerebral Infarction - physiopathology
Deoxyuracil Nucleotides
DNA Fragmentation
Edema - physiopathology
Evans Blue - pharmacokinetics
Ischemic Attack, Transient - enzymology
Ischemic Attack, Transient - mortality
Ischemic Attack, Transient - physiopathology
Mice
Mice, Mutant Strains
Neurologic Examination
Neurons - enzymology
Neurons - pathology
Oxidative Stress - physiology
Prosencephalon - blood supply
Prosencephalon - enzymology
Prosencephalon - pathology
Reactive Oxygen Species - physiology
Staining and Labeling
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
title Reduction of CuZn-Superoxide Dismutase Activity Exacerbates Neuronal Cell Injury and Edema Formation after Transient Focal Cerebral Ischemia
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