Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency
Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency
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DOI：
10.1161/01.str.30.9.1962
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发表时间：
1999-09-01
期刊：
影响因子：
8.3
通讯作者：
Chan, PH
中科院分区：
文献类型：
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作者：
Kawase, M;Murakami, K;Chan, PH
背景和目的：我们已经证明，铜锌超氧化物歧化酶（CuZn-SOD），一种SOD的胞浆同工酶，在超氧化物自由基介导的脑损伤的发病机制中具有保护作用。本研究采用CuZn-SOD基因（Sod 1）缺失的小鼠，旨在阐明超氧阴离子在短暂性全脑缺血后选择性易损性发病机制中的作用。（Sod 1-/-）与完全缺乏内源性CuZn-SOD活性，杂合子突变小鼠（Sod 1 +/-），活性降低50%，并对同窝野生型小鼠（雄性，35至45 g）进行全脑缺血。由于后交通动脉（PcomA）的可塑性已被报道影响海马损伤的结果，我们评估了PcomA的可塑性与全脑缺血时局部脑血流量减少之间的关系。与野生型小鼠相比，突变型小鼠在全脑缺血5分钟和10分钟后1天增加。PcomA发育不良大脑中的海马损伤在全脑缺血5分钟后3天与野生型同窝小鼠相比，突变小鼠的海马损伤显着恶化，尽管在1天时没有观察到显着差异。结论-这些数据表明超氧自由基在短暂性全脑缺血后脆弱的海马CAI亚区延迟损伤的发病机制中发挥着重要作用。
Background and Purpose-We have demonstrated that copper-zinc superoxide dismutase (CuZn-SOD), a cytosolic isoenzyme of SODs, has a protective role in the pathogenesis of superoxide radical-mediated brain injury. Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia.Methods-Sod1 knockout homozygous mutant mice (Sod1 -/-) with a complete absence of endogenous CuZn-SOD activity, heterozygous mutant mice (Sod1 +/-) with a 50% decrease in the activity, and littermate wild-type mice (male, 35 to 45 g) were subjected to global ischemia. Since the plasticity of the posterior communicating artery (PcomA) has been reported to influence the outcome of hippocampal injury, we assessed the relation between the plasticity of PcomAs and the decrease of regional cerebral blood flow in global ischemia.Results-The fluorescence intensity of hydroethidine oxidation, a measurement of ethidium fluorescence for superoxide radicals, was increased in mutant mice 1 day after both 5 and 10 minutes of global ischemia, compared with wild-type mice. Hippocampal injury in the PcomA hypoplastic brains showed significant exacerbation in mutant mice compared with wild-type littermates 3 days after 5 minutes of global ischemia, although a marked difference was not observed at 1 day.Conclusions-These data suggest that superoxide radicals play an important role in the pathogenesis of delayed injury in the vulnerable hippocampal CAI subregion after transient global ischemia.