Amelioration of mitochondrial function by a novel antioxidant U-101033E following traumatic brain injury in rats.
Amelioration of mitochondrial function by a novel antioxidant U-101033E following traumatic brain injury in rats.
复制标题
新型抗氧化剂 U-101033E 在大鼠脑外伤后改善线粒体功能。
作者：
Y. Xiong;P. Peterson;J. Muizelaar;C. Lee
在本研究中，一个严重的创伤性脑损伤（TBI）的大鼠右顶叶皮层使用控制皮质撞击损伤（CCII）模型。脑损伤后12-72 h，损伤半球分离的前脑线粒体的钙稳态受到干扰，电子传递和能量耦合活性受损。评价了血脑屏障穿透性抗氧化剂U-101033 E对TBI诱导的线粒体损伤的功效。在剂量反应实验中，在TBI后5分钟和2小时给予两次静脉推注（溶媒或1-10 mg/kg U-101033 E）。在损伤后12小时检查来自每个半球的前脑线粒体。关于前脑线粒体功能障碍，药物显示出钟形剂量-反应曲线，最佳剂量为3 mg/kg（n = 5，p < 0.05，相对于媒介物）。在时程实验中，在损伤后5 min和2 h分别静脉注射两次3 mg U-101033 E/kg（最佳剂量），并在损伤后6 h-14 d检查前脑线粒体。U-101033 E在伤后6 h至14 d显著恢复电子传递、能量耦合能力和Ca 2+转运能力。我们的数据表明，抗氧化剂U-101033 E在损伤后给予适当剂量可以有效地恢复TBI诱导的线粒体功能障碍，并支持氧化应激在TBI的发病机制中起着重要作用的论点。
In the present study, a severe traumatic brain injury (TBI) was produced over the right parietal cortex of rats using the controlled cortical impact injury (CCII) model. TBI perturbed calcium homeostasis and impaired electron transfer and energy coupling activities of forebrain mitochondria isolated from injured hemispheres with a maximal injury at 12-72 h. Efficacy of the blood-brain barrier penetrating antioxidant U-101033E on TBI-induced mitochondrial impairment was evaluated. In the dose-response experiment, two i.v. boluses (vehicle or 1-10 mg/kg of U-101033E) were administered at 5 min and 2h post-TBI. Forebrain mitochondria from each hemisphere were examined at 12 h post-injury. With respect to forebrain mitochondrial dysfunction, the drug showed a bell-shaped dose-response curve with an optimal dose of 3 mg/kg (n = 5, p < 0.05 vs. vehicle). In the time-course experiment, two i.v. boluses of 3 mg U-101033E/kg (the optimal dose) were given at 5 min and 2 h post-injury and forebrain mitochondria were examined at 6 h-14 days post-injury. U-101033E significantly restored electron transfer, energy coupling capacity, and Ca2+ transport capacity during 6 h to 14 days post-injury. Our data indicate that the antioxidant U-101033E administered post-injury at proper dosage can effectively restore TBI-induced mitochondrial dysfunction and support the contention that oxidative stress plays an important role in the pathogenesis of TBI.
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影响因子：
4.1
作者：
Yang,MS;DeWitt,DS;Becker,DP;Hayes,RL
通讯作者：
Hayes,RL
DOI：
10.1089/cns.1986.3.257
发表时间：
1986
期刊：
Central nervous system trauma : journal of the American Paralysis Association
影响因子：
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作者：
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通讯作者：
H. Kontos;J. Povlishock
影响因子：
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作者：
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DARBY, JM
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DOI：
10.1016/0167-4889(92)90180-j
发表时间：
1992
期刊：
Biochimica et biophysica acta
影响因子：
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作者：
Sciamanna,MA;Zinkel,J;Fabi,AY;Lee,CP
通讯作者：
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