Mori T, Kawamata T, Katayama Y, Maeda T, Aoyama N, Kikuchi T, Uwahodo Y
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Acta Neurochir Suppl. 1998;71:120-2. doi: 10.1007/978-3-7091-6475-4_36.
Oxygen free radicals contribute to various kinds of tissue injury processes within the central nervous system. It has been suggested that inhibition of free radical formation has the potential to attenuate secondary neural tissue damage involving ischemia or trauma, and antioxidant therapy may offer a promising approach. In the present study, employing a cortical contusion model in the rat, contusion-induced neural damage, was evaluated by investigating edema formation, behavioral activities and histological changes. The effects of the superoxide radical scavenger, OPC-14117, were also tested to determine how free radicals may contribute to such neural damage. The results demonstrated that cerebral contusion induces a progressive decrease in tissue specific gravity representing edema formation, and behavioral deficits in the Morris water maze test and habituation of exploratory activity. Histological examinations revealed necrotic cavity formation in the cortex and selective neuronal death of the hippocampal CA3 region. These changes were significantly attenuated by OPC-14117, which was administered as a single dose immediately following trauma induction. The above results indicate that oxygen free radicals are involved in contusion-induced edema formation, subsequent tissue damage and cognitive deficits. The superoxide radical scavenger, OPC-14117, has a powerful therapeutic potential for preventing secondary cell damage following traumatic brain injury.
氧自由基参与中枢神经系统内的各种组织损伤过程。有人提出，抑制自由基形成有可能减轻涉及缺血或创伤的继发性神经组织损伤，抗氧化治疗可能是一种有前景的方法。在本研究中，采用大鼠皮质挫伤模型，通过研究水肿形成、行为活动和组织学变化来评估挫伤诱导的神经损伤。还测试了超氧阴离子自由基清除剂OPC-14117的作用，以确定自由基如何导致这种神经损伤。结果表明，脑挫伤导致代表水肿形成的组织比重逐渐降低，以及在莫里斯水迷宫试验中的行为缺陷和探索活动的习惯化。组织学检查显示皮质出现坏死腔形成以及海马CA3区神经元选择性死亡。这些变化在创伤诱导后立即单次给予OPC-14117后得到显著减轻。上述结果表明，氧自由基参与挫伤诱导的水肿形成、随后的组织损伤和认知缺陷。超氧阴离子自由基清除剂OPC-14117在预防创伤性脑损伤后的继发性细胞损伤方面具有强大的治疗潜力。
