Manganese Superoxide Dismutase Deficiency Exacerbates Cerebral Infarction After Focal Cerebral Ischemia/Reperfusion in Mice
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- Gyung W. Kim
- From the Department of Neurosurgery, Department of Neurology & Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.
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- Takeo Kondo
- From the Department of Neurosurgery, Department of Neurology & Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.
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- Nobuo Noshita
- From the Department of Neurosurgery, Department of Neurology & Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.
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- Pak H. Chan
- From the Department of Neurosurgery, Department of Neurology & Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, Calif.
書誌事項
- タイトル別名
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- Implications for the Production and Role of Superoxide Radicals
抄録
<jats:p> <jats:bold> <jats:italic> <jats:bold> <jats:italic>Background and Purpose</jats:italic> </jats:bold> — </jats:italic> </jats:bold> Superoxide anion radicals (O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> ) are implicated in ischemia/reperfusion injury, although a direct relationship has not been elucidated. Recently, a specific method of hydroethidine (HEt) oxidation by O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> was developed to detect O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production in a variety of experimental brain injury models. To clarify the role of O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> in the mechanism of ischemia/reperfusion, we investigated O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production after ischemia/reperfusion and ischemia/reperfusion injury in mutant mice deficient in mitochondrial manganese superoxide dismutase (MnSOD) and in wild-type littermates. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:bold> <jats:italic>Methods</jats:italic> </jats:bold> — </jats:italic> </jats:bold> Ischemia/reperfusion was performed for 60 minutes using intraluminal suture blockade of the middle cerebral artery in the mutant or wild-type mice. We evaluated fluorescent kinetics of HEt or ethidium, the oxidized form of HEt, in brains after an intravenous injection of HEt, followed by measurement of cellular O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production using specific HEt oxidation by O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> before and after ischemia/reperfusion. Furthermore, we compared O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production and subsequent infarct volume in the mice using triphenyltetrazolium chloride after ischemia/reperfusion. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:bold> <jats:italic>Results</jats:italic> </jats:bold> — </jats:italic> </jats:bold> HEt oxidation to ethidium is primarily a result of mitochondrially produced O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> under physiological conditions. Cerebral ischemia/reperfusion produced O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> prominently in neurons shortly after reperfusion, followed by a delayed increase in endothelial cells. A deficiency in MnSOD in mutant mice increased mitochondrial O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production and exacerbated cerebral infarction, worsening neurological deficits after ischemia/reperfusion. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:bold> <jats:italic>Conclusion</jats:italic> </jats:bold> — </jats:italic> </jats:bold> These results suggest that mitochondrial O <jats:sub>2</jats:sub> <jats:sup>·−</jats:sup> production may be a critical step underlying the mechanism of ischemia/reperfusion injury and that MnSOD may protect against ongoing oxidative cell death after ischemia/reperfusion. </jats:p>
収録刊行物
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- Stroke
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Stroke 33 (3), 809-815, 2002-03
Ovid Technologies (Wolters Kluwer Health)
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詳細情報 詳細情報について
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- CRID
- 1362825895786533248
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- NII論文ID
- 30022679229
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- ISSN
- 15244628
- 00392499
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