Kawamata T, Katayama Y, Maeda T, Mori T, Aoyama N, Kikuchi T, Uwahodo Y
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Acta Neurochir Suppl. 1997;70:191-3. doi: 10.1007/978-3-7091-6837-0_59.
Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.
氧自由基可能在缺血或创伤后参与中枢神经系统的组织损伤过程。最近的研究表明，在涉及此类情况的实验模型中，抑制自由基可改善结果，抗氧化治疗似乎很有前景。在本研究中，对大鼠皮质挫伤模型中的行为变化和水肿形成进行了研究，并测试了超氧自由基清除剂OPC-14117的作用。用氟烷吸入麻醉Wistar大鼠。使用可控皮质撞击装置在顶叶皮质诱导皮质挫伤。损伤诱导后立即给予OPC-14117（300mg/kg，口服）。通过比重法评估挫伤中心和周边区域的水肿形成。通过莫里斯水迷宫试验和探索活动的习惯化来评估行为变化。结果显示，给予赋形剂的对照组在损伤后出现渐进性水肿形成和行为缺陷。OPC-14117治疗可显著减轻这些变化（p<0.05）。此外，OPC-14117减小了挫伤性坏死的大小（p<0.05）。这些发现表明，超氧自由基参与挫伤诱导的水肿形成、坏死形成和行为缺陷，并且OPC-14117具有预防创伤性脑损伤后继发性细胞损伤的治疗潜力。
