Free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism. Imbalance between cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress (OS). OS has been implicated as a potential contributor to the pathogenesis of acute central nervous system (CNS) injury. After brain injury by ischemic or hemorrhagic stroke or trauma, the production of reactive oxygen species (ROS) may increase, sometimes drastically, leading to tissue damage via several different cellular molecular pathways. Radicals can cause damage to cardinal cellular components such as lipids, proteins, and nucleic acids (e.g., DNA), leading to subsequent cell death by modes of necrosis or apoptosis. The damage can become more widespread due to weakened cellular antioxidant defense systems. Moreover, acute brain injury increases the levels of excitotoxic amino acids (such as glutamate), which also produce ROS, thereby promoting parenchymatous destruction. Therefore, treatment with antioxidants may theoretically act to prevent propagation of tissue damage and improve both the survival and neurological outcome. Several such agents of widely varying chemical structures have been investigated as therapeutic agents for acute CNS injury. Although a few of the antioxidants showed some efficacy in animal models or in small clinical studies, these findings have not been supported in comprehensive, controlled trials in patients. Reasons for these equivocal results may include, in part, inappropriate timing of administration or suboptimal drug levels at the target site in CNS. Better understanding of the pathological mechanisms of acute CNS injury would characterize the exact primary targets for drug intervention. Improved antioxidant design should take into consideration the relevant and specific harmful free radical, blood brain barrier (BBB) permeability, dose, and time administration. Novel combinations of drugs providing protection against various types injuries will probably exploit the potential synergistic effects of antioxidants in stroke.

中文翻译：

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在急性中枢神经系统损伤中的抗氧化治疗：当前状态。

自由基是主要在细胞呼吸和正常代谢过程中产生的高反应性分子。细胞的自由基产生与细胞防御自由基的能力之间的不平衡称为氧化应激（OS）。OS已经被认为是急性中枢神经系统（CNS）损伤的发病机理的潜在贡献者。在缺血性或出血性中风或创伤导致脑损伤后，活性氧（ROS）的产生可能会增加，有时会急剧增加，从而通过几种不同的细胞分子途径导致组织损伤。自由基可导致对主要细胞成分（如脂质，蛋白质和核酸（例如DNA））的破坏，从而导致细胞通过坏死或凋亡的方式死亡。由于细胞抗氧化剂防御系统的削弱，这种损害可能变得更加广泛。此外，急性脑损伤会增加兴奋性氨基酸（例如谷氨酸）的水平，后者也会产生ROS，从而促进实质性破坏。因此，用抗氧化剂进行治疗在理论上可以防止组织损伤的扩散，并改善存活率和神经系统的预后。已经研究了具有广泛变化的化学结构的几种这样的试剂作为急性CNS损伤的治疗剂。尽管一些抗氧化剂在动物模型或小型临床研究中显示出某些功效，但这些发现并未在患者的全面对照试验中得到支持。这些模棱两可的结果的部分原因可能包括：在CNS的目标部位给药时间不适当或药物水平欠佳。更好地了解急性中枢神经系统损伤的病理机制将成为药物干预的确切主要靶点。改进的抗氧化剂设计应考虑相关和特定的有害自由基，血脑屏障（BBB）渗透性，剂量和给药时间。提供针对各种类型伤害的保护的新型药物组合可能会利用中风中抗氧化剂的潜在协同作用。血脑屏障（BBB）的渗透性，剂量和给药时间。提供针对各种类型伤害的保护的新型药物组合可能会利用中风中抗氧化剂的潜在协同作用。血脑屏障（BBB）的渗透性，剂量和给药时间。提供对抗各种类型伤害的保护作用的新型药物组合可能会利用中风中抗氧化剂的潜在协同作用。