Edema formation exacerbates neurological and histological outcomes after focal cerebral ischemia in CuZn-superoxide dismutase gene knockout mutant mice.
Edema formation exacerbates neurological and histological outcomes after focal cerebral ischemia in CuZn-superoxide dismutase gene knockout mutant mice.
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CuZn-超氧化物歧化酶基因敲除突变小鼠局灶性脑缺血后，水肿形成加剧神经学和组织学结果。
DOI：
10.1007/978-3-7091-6837-0_19
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Chan,PH
中科院分区：
文献类型：
--
作者：
Kondo,T;Reaume,AG;Huang,TT;Murakami,K;Carlson,E;Chen,S;Scott,RW;Epstein,CJ;Chan,PH
在各种研究中，铜锌超氧化物歧化酶（CuZn-SOD）已被证明可以防止缺血性脑损伤。CuZn-SOD抑制各种神经损伤后脑水肿的形成，这一发现表明CuZn-SOD相关的神经元活力调节可能发挥作用。我们评估了CuZn-SOD对小鼠局灶性脑缺血后脑水肿形成的作用。纯合突变体（Sod 1-/-）没有检测到CuZn-SOD活性和杂合突变体（Sod 1 +/-）显示了50%的下降相比，野生型小鼠。Sod 1-/-小鼠在大脑中动脉闭塞1小时后不久表现出高水平的血脑屏障（BBB）破坏，缺血后24小时死亡率为100%。Sod 1 +/-小鼠表现出中等水平的BBB破坏和30%的死亡率。Sod 1 +/-动物的梗死体积和脑肿胀增加，伴随缺血后24小时神经功能缺损加重。这些结果表明超氧阴离子在局灶性脑缺血后脑水肿的发展中的重要作用，并建议脑水肿的形成可能有助于缺血性脑损伤和基因敲除突变小鼠的神经功能缺损的加重。
In a variety of studies, CuZn-superoxide dismutase (CuZn-SOD) has been shown to protect against ischemic brain injury. A possible role for CuZn-SOD-related modulation of neuronal viability has been suggested by the finding that CuZn-SOD inhibits brain edema formation following various kinds of neurological insults. We have evaluated the role of CuZn-SOD on brain edema formation following focal cerebral ischemia in mice bearing a disruption of the CuZn-SOD gene (Sod1). Homozygous mutants (Sod1-/-) had no detectable CuZn-SOD activity and heterozygous mutants (Sod1+/-) showed a 50% decrease compared to wild-type mice. Sod1-/-mice showed a high level of blood-brain barrier (BBB) disruption shortly after 1 hr of middle cerebral artery occlusion and 100% mortality at 24 hr following ischemia. Sod1+/-mice showed a moderate level of BBB disruption and 30% mortality. The Sod1+/-animals had increased infarct volume and brain swelling, accompanying exacerbated neurological deficits at 24 hr following ischemia. These results indicate the important role of superoxide anions in the development of brain edema after focal cerebral ischemia and suggest the possibility that brain edema formation may contribute to the exacerbation of ischemic brain injury and neurological deficits in knockout mutant mice.