Baranova Anna I, Whiting Mark D, Hamm Robert J
Department of Psychology, Virginia Commonwealth University, Richmond, VA 23284-2018, USA.
J Neurotrauma. 2006 Aug;23(8):1233-40. doi: 10.1089/neu.2006.23.1233.
Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.
慢性认知障碍是人类和动物创伤性脑损伤(TBI)的一个持久特征。在损伤后的创伤阶段治疗认知障碍通常涉及给予针对特定神经递质系统的药物。当前的研究考察了促智药阿尼西坦对大鼠TBI后认知恢复的影响。进行了三项实验以确定:(1)治疗认知障碍的阿尼西坦最佳剂量;(2)TBI后延迟数天进行药物治疗的效果;(3)在认知评估前终止药物治疗的效果。在实验1中,给大鼠施加中度液体冲击伤,并给予赋形剂、25或50mg/kg阿尼西坦治疗15天。在损伤后第11 - 15天测量时,两种剂量的阿尼西坦均有效减轻了损伤诱导的莫里斯水迷宫(MWM)缺陷。在实验2中,受伤大鼠在损伤后第11天开始用50mg/kg阿尼西坦或赋形剂治疗,并持续15天。在第26 - 30天评估的MWM表现表明,接受阿尼西坦治疗的动物表现与假损伤对照组一样好。在实验3中,动物受伤并用阿尼西坦治疗15天。在损伤后第16 - 20天的MWM测试期间终止药物治疗。在该实验中,接受阿尼西坦治疗的大鼠表现并不比接受赋形剂治疗的大鼠更好。这些实验结果表明,阿尼西坦是TBI诱导的认知障碍的有效治疗方法,即使在损伤后延迟数天进行治疗也是如此。