Shear Deborah A, Williams Anthony J, Sharrow Keith, Lu Xi-Chun M, Tortella Frank C
Walter Reed Army Institute of Research, Department of Applied Neurobiology, Silver Spring, MD 21045, USA.
Pharmacol Biochem Behav. 2009 Nov;94(1):56-62. doi: 10.1016/j.pbb.2009.07.006. Epub 2009 Jul 17.
Dextromethorphan (DM) has been well-characterized as a neuroprotective agent in experimental models of CNS injury. The goal of this study was to determine the neuroprotective profile of DM in a military-relevant model of penetrating ballistic-like brain injury (PBBI). In an acute (3 day) dose-response study, anesthetized male Sprague-Dawley rats were exposed to a unilateral frontal PBBI with DM (0.156-10 mg/kg) or vehicle delivered as an i.v. bolus from 30 min to 48 h post-injury. In a follow-up (7 day) experiment, the 10-mg/kg bolus injections of DM were administered in conjunction with a 6-h infusion (5 mg/kg/h). DM bolus injections alone produced a dose-dependent improvement in motor recovery on a balance beam task at 3 days post-injury. However, more rapid recovery (24 h) was observed on this task when the bolus injections were combined with the 6-h infusion. Moreover, the DM bolus/infusion treatment regimen resulted in a significant (76%) improvement in cognitive performance in a novel object recognition (NOR) task at 7 days post-injury. Although post-injury administration of DM (all doses) failed to reduce core lesion size, the maximum dose of DM (10 mg/kg) was effective in reducing silver-stained axonal fiber degeneration in the cortical regions adjacent to the injury.
右美沙芬（DM）在中枢神经系统损伤的实验模型中已被充分表征为一种神经保护剂。本研究的目的是确定DM在与军事相关的穿透性弹道样脑损伤（PBBI）模型中的神经保护作用。在一项急性（3天）剂量反应研究中，将麻醉的雄性Sprague-Dawley大鼠暴露于单侧额叶PBBI，在损伤后30分钟至48小时静脉推注DM（0.156 - 10毫克/千克）或赋形剂。在一项后续（7天）实验中，以10毫克/千克的剂量静脉推注DM，并同时进行6小时的输注（5毫克/千克/小时）。单独静脉推注DM在损伤后3天的平衡木任务中产生了剂量依赖性的运动恢复改善。然而，当静脉推注与6小时输注相结合时，在该任务中观察到更快的恢复（24小时）。此外，DM静脉推注/输注治疗方案在损伤后7天的新物体识别（NOR）任务中导致认知表现显著改善（76%）。尽管损伤后给予DM（所有剂量）未能减小核心损伤大小，但DM的最大剂量（10毫克/千克）有效地减少了损伤附近皮质区域的银染轴突纤维变性。
