Lyeth B G, Dixon C E, Jenkins L W, Hamm R J, Alberico A, Young H F, Stonnington H H, Hayes R L
Richard Roland Reynolds Neurosurgical Research Laboratories, Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Brain Res. 1988 Jun 14;452(1-2):39-48. doi: 10.1016/0006-8993(88)90006-6.
Scopolamine (0.1, 1.0, or 10.0 mg/kg) or saline was systemically (i.p.) administered to rats 15 min prior to concussive fluid percussion brain injury. Animals pretreated with the 1.0 mg/kg dose exhibited significantly (P less than 0.05) less motor deficits and less body weight loss and recovered to baseline performance sooner than saline-treated rats. Mortality and associated convulsions were significantly lower in rats pretreated with the 1.0 mg/kg dose of scopolamine. A 1.0 mg/kg dose of scopolamine administered (i.p.) 30 s after injury also significantly reduced behavioral deficits. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea following injury. A 1.0 mg/kg dose of scopolamine administered (i.p.) 15 min prior to epidural clip compression of the spinal cord had no effect on the severity of motor function deficits assessed by an inclined plane test. The data from these experiments suggest muscarinic cholinergic involvement in at least some of the long-term behavioral deficits following mild and moderate levels of brain injury. These results suggest that muscarinic cholinergic antagonists may prove beneficial in the treatment of human head injury.
在进行冲击性液体脑损伤前15分钟，给大鼠腹腔注射东莨菪碱（0.1、1.0或10.0毫克/千克）或生理盐水。用1.0毫克/千克剂量预处理的动物与生理盐水处理的大鼠相比，运动功能障碍显著减轻（P小于0.05），体重减轻更少，且恢复到基线水平的速度更快。用1.0毫克/千克剂量东莨菪碱预处理的大鼠死亡率和相关惊厥显著降低。在损伤后30秒腹腔注射1.0毫克/千克剂量的东莨菪碱也显著减轻了行为缺陷。在损伤后短暂呼吸暂停的发生率或持续时间方面，生理盐水处理组和东莨菪碱处理组动物之间未观察到差异。在硬膜外夹闭脊髓前15分钟腹腔注射1.0毫克/千克剂量的东莨菪碱，对通过斜面试验评估的运动功能障碍严重程度没有影响。这些实验数据表明，毒蕈碱胆碱能系统至少参与了轻度和中度脑损伤后的一些长期行为缺陷。这些结果表明，毒蕈碱胆碱能拮抗剂可能对治疗人类头部损伤有益。
