Antioxidant therapies in traumatic brain and spinal cord injury.
Antioxidant therapies in traumatic brain and spinal cord injury.
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DOI：
10.1016/j.bbadis.2011.10.017
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Hall ED
中科院分区：
文献类型：
--
作者：
Bains M;Hall ED
自由基形成和氧化损伤已被广泛研究和验证为急性中枢神经系统损伤的病理生理学的重要贡献者。活性氧（ROS）和活性氮（RNS）的产生是机械冲击数分钟内发生损伤后的早期事件。在这种情况下的一个关键组成部分是过氧亚硝酸盐诱导的脂质过氧化。正如本文所讨论的，过氧亚硝酸盐的形成和脂质过氧化不可逆地损害神经元膜脂质和蛋白质功能，从而导致随后的离子稳态，谷氨酸介导的兴奋性毒性，线粒体呼吸衰竭和微血管损伤的破坏。抗氧化方法包括抑制和/或清除超氧化物、过氧亚硝酸盐或羰基化合物，抑制脂质过氧化和靶向内源性抗氧化防御系统。本文综述了支持ROS和RNS及其衍生的氧自由基在急性创伤性脑损伤（TBI）和脊髓损伤（SCI）后继发性损伤反应中的作用的临床前和临床文献，并回顾了过去和当前抗氧化治疗策略的发展趋势。与建议的机制互补的抗氧化剂的组合治疗也将被讨论作为一个有前途的神经保护方法在TBI和SCI治疗研究。本文是特刊的一部分，题为：抗氧化剂和抗氧化剂治疗疾病。
Free radical formation and oxidative damage have been extensively investigated and validated as important contributors to the pathophysiology of acute central nervous system injury. The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following injury occurring within minutes of mechanical impact. A key component in this event is peroxynitrite-induced lipid peroxidation. As discussed in this review, peroxynitrite formation and lipid peroxidation irreversibly damages neuronal membrane lipids and protein function, which results in subsequent disruptions in ion homeostasis, glutamate-mediated excitotoxicity, mitochondrial respiratory failure and microvascular damage. Antioxidant approaches include the inhibition and/or scavenging of superoxide, peroxynitrite, or carbonyl compounds, the inhibition of lipid peroxidation and the targeting of the endogenous antioxidant defense system. This review covers the preclinical and clinical literature supporting the role of ROS and RNS and their derived oxygen free radicals in the secondary injury response following acute traumatic brain injury (TBI) and spinal cord injury (SCI) and reviews the past and current trends in the development of antioxidant therapeutic strategies. Combinatorial treatment with the suggested mechanistically complementary antioxidants will also be discussed as a promising neuroprotective approach in TBI and SCI therapeutic research. This article is part of a Special Issue entitled: Antioxidants and antioxidant treatment in disease.
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