Clifton G L, Lyeth B G, Jenkins L W, Taft W C, DeLorenzo R J, Hayes R L
Department of Surgery, Richard Roland Reynolds Neurosurgical Research Laboratories, Richmond, Virginia.
J Neurotrauma. 1989;6(2):71-81. doi: 10.1089/neu.1989.6.71.
One hundred and one rats were administered either D, alpha-tocopheryl succinate plus polyethylene glycol (PEG), PEG, or saline 30 min prior to or 5 min after moderate fluid percussion brain injury. Mortality rates, performance on beam balance and beam-walking tasks, and body weight were assessed daily for 10 days. With preinjury administration, mortality rate was reduced from 31% with saline to 9% with PEG and 9% with D, alpha-tocopheryl succinate plus PEG. With postinjury administration, mortality rate was reduced from 36% with saline to 20% with PEG and to 10% with the D, alpha-tocopheryl succinate plus PEG combination. With administration prior to injury, PEG and D, alpha-tocopheryl succinate plus PEG reduced the deficits seen on beam balance testing on days 1-3 after injury. On beam walking, PEG and D, alpha-tocopheryl succinate plus PEG reduced deficits compared to those in saline-injected animals on days 1 and 2 and on day 1 after injury, respectively. A strongly protective effect of PEG and of D, alpha-tocopheryl succinate plus PEG was seen with preinjury administration. With postinjury administration, D, alpha-tocopheryl succinate plus PEG reduced deficits on beam balance testing compared to animals receiving both saline and PEG on days 1-3 after injury. On beam-walking latencies, D, alpha-tocopheryl succinate plus PEG reduced deficits on days 1 and 2 after injury compared to saline and to PEG. Both PEG and D, alpha-tocopheryl succinate plus PEG reduced weight loss after injury compared to saline. The protective effects of these agents and their relatively low toxicity and high lipid solubility give them potential for the treatment of human head injury.
101只大鼠在中度液压颅脑损伤前30分钟或损伤后5分钟,分别给予维生素E琥珀酸酯加聚乙二醇(PEG)、PEG或生理盐水。连续10天每天评估死亡率、在平衡木和走平衡木任务中的表现以及体重。损伤前给药时,死亡率从生理盐水组的31%降至PEG组的9%和维生素E琥珀酸酯加PEG组的9%。损伤后给药时,死亡率从生理盐水组的36%降至PEG组的20%和维生素E琥珀酸酯加PEG组合组的10%。损伤前给药时,PEG和维生素E琥珀酸酯加PEG减少了损伤后第1 - 3天平衡木测试中出现的功能缺陷。在走平衡木方面,与注射生理盐水的动物相比,PEG和维生素E琥珀酸酯加PEG分别在损伤后第1天和第2天以及第1天减少了功能缺陷。损伤前给药时,PEG和维生素E琥珀酸酯加PEG显示出强大的保护作用。损伤后给药时,与损伤后第1 - 3天接受生理盐水和PEG的动物相比,维生素E琥珀酸酯加PEG减少了平衡木测试中的功能缺陷。在走平衡木潜伏期方面,与生理盐水和PEG相比,维生素E琥珀酸酯加PEG在损伤后第1天和第2天减少了功能缺陷。与生理盐水相比,PEG和维生素E琥珀酸酯加PEG都减少了损伤后的体重减轻。这些药物的保护作用以及它们相对较低的毒性和高脂质溶解性使其具有治疗人类头部损伤的潜力。