Ikeda Y, Brelsford K L, Ikeda K, Long D M
Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Neurol Res. 1989 Dec;11(4):213-6. doi: 10.1080/01616412.1989.11739895.
Oxygen-free radicals have been implicated as causative factors in ischaemic and traumatic processes. Oxygen-free radical scavengers can be used potentially to treat brain oedema. We investigated the effects of superoxide dismutase and dimethylthiourea on brain oedema. Vasogenic brain oedema was produced in 44 cats by a cortical freezing lesion. Animals were separated into three groups: (1) cold-induced oedema with sacrifice at 6, 24 and 48 h; (2) cold-induced oedema with sacrifice at 6, 24 and 48 h: subgroup A was pretreated with 10,000 u./kg polyethylene glycol and superoxide dismutase; subgroup B received a bolus injection of free superoxide dismutase (4 mg/kg) and then 1 mg/kg/min for 20 min; (3) cold-induced oedema with sacrifice at 6 and 24 h: this group was pretreated with 500 mg/kg dimethylthiourea. Brain water content was measured by the specific gravity method. Detection of superoxide radicals was carried out by the direct cortical application of nitroblue tetrazolium. Free and polyethylene glycol-superoxide dismutase did not prevent the development of brain oedema, but superoxide radicals were detected in the cold lesion. Dimethylthiourea prevented the development of brain oedema in the white matter adjacent to the lesion at 6 h but not at 24 h. These findings indicate that oxygen-free radicals are generated by the brain following cold injury and the demonstration of these radicals offers an important clue in the genesis of traumatic brain oedema.
氧自由基被认为是缺血和创伤过程中的致病因素。氧自由基清除剂有可能用于治疗脑水肿。我们研究了超氧化物歧化酶和二甲基硫脲对脑水肿的影响。通过皮层冷冻损伤在44只猫中产生血管源性脑水肿。动物被分为三组:(1)冷诱导性水肿,分别在6小时、24小时和48小时处死;(2)冷诱导性水肿,分别在6小时、24小时和48小时处死:A亚组用10,000单位/千克聚乙二醇和超氧化物歧化酶预处理;B亚组先静脉推注游离超氧化物歧化酶(4毫克/千克),然后以1毫克/千克/分钟的速度注射20分钟;(3)冷诱导性水肿,分别在6小时和24小时处死:该组用500毫克/千克二甲基硫脲预处理。采用比重法测量脑含水量。通过将硝基蓝四唑直接应用于皮层来检测超氧自由基。游离的和聚乙二醇化超氧化物歧化酶不能阻止脑水肿的发展,但在冷损伤部位检测到了超氧自由基。二甲基硫脲在6小时时可阻止损伤灶附近白质脑水肿的发展,但在24小时时则不能。这些发现表明,脑在冷损伤后会产生氧自由基,而这些自由基的证实为创伤性脑水肿的发生提供了重要线索。