Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice
Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice
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DOI：
10.3171/jns.1996.85.5.0885
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发表时间：
1996-11-01
影响因子：
4.1
通讯作者：
Chan, PH
中科院分区：
文献类型：
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作者：
Mikawa, S;Kinouchi, H;Chan, PH
为了阐明氧自由基和超氧化物歧化酶在创伤性脑损伤（TBI）中的作用，使用非转基因（nTg）小鼠和1.5- 1.5 μ g/ml的杂合和纯合转基因（Tg）小鼠在TBI后评价血脑屏障（BBB）通透性、脑水肿、行为功能和坏死腔体积（CV）。人铜锌超氧化物歧化酶（CuZn-SOD）活性分别升高1.5倍（Tg1.5x）、3.1倍（Tg3.1x）和5倍（Tg 5x）。伤后4小时Evans蓝染料渗漏以CuZn-SOD剂量依赖性方式减少，Tg1.5x、Tg3.1x和Tg 5x组分别减少18.6%、40.9%和48.8%。TE3.1x组和Tg 5x组伤后6小时的含水量（79.64%和79.45%）显著低于nTg组（81.37%）。在TBI后1天，通过平衡木行走和平衡木平衡任务测量，体重和运动性能最初下降。然而，Tg小鼠的平衡木和平衡木行走性能缺陷的平均减少和损伤后体重的变化显著改善。Tg小鼠的CV显著小于nTg小鼠（p < 0.01）。这些结果表明，超氧自由基在TRI后发挥着有害作用。此外，Tg小鼠提供了一种有用的模型，用于证明抗氧化酶在TBI中的有益作用，而没有与外源性试剂相关的药代动力学、毒性和BBB通透性的混杂效应。
To elucidate the role of oxygen-derived free radicals and superoxide dismutase in traumatic brain injury (TBI), blood-brain barrier (BBB) permeability, brain edema, behavioral function, and necrotic cavity volume (CV) were evaluated after TBI using nontransgenic (nTg) mice and heterozygous and homozygous transgenic (Tg) mice with a 1.5-(Tg1.5x), 3.1-(Tg3.1x) and five-(Tg5x) fold increase in human copper, zinc-superoxide dismutase (CuZn-SOD) activity.Traumatic brain injury was produced by the weight-drop method. Evans blue dye leakage 4 hours after injury was attenuated in a CuZn-SOD dose-dependent manner with decreases of 18.6%, 40.9%, and 48.8%, in the Tg1.5x, Tg3.1x, and Tg5x groups, respectively. The water content 6 hours after injury in the TE3.1x (79.64%) and Tg5x (79.45%) groups was significantly lower than in nTg mice (81.37%). There was an initial decrease in body weight and in motor performance, as measured by beam walk and beam balance tasks undertaken 1 day after TBI. However, the average reduction in beam balance and beam walk performance deficits and changes in body weight postinjury were significantly ameliorated in Tg mice. The CV was significantly smaller in Tg mice than in nTg mice (p < 0.01). These results indicate that superoxide radicals play a deleterious role following TRI. Furthermore, Tg mice provide a useful model for demonstrating the beneficial role of an antioxidant enzyme in TBI without the confounding effect of pharmacokinetics, toxicity, and BBB per meability associated with exogenous agents.