Hoane Michael R, Tan Arlene A, Pierce Jeremy L, Anderson Gail D, Smith Douglas C
Restorative Neuroscience Laboratory, Department of Psychology, Southern Illinois University, Carbondale, Illinois 62901, USA.
J Neurotrauma. 2006 Oct;23(10):1535-48. doi: 10.1089/neu.2006.23.1535.
This study examined the ability of nicotinamide (vitamin B3) to improve functional outcome in a dose-dependent manner following fluid percussion injury (FPI). Injured (duration of unconsciousness mean = 85.8 sec; apnea = 9.9 sec), rats were administered nicotinamide (500 or 50 mg/kg; ip) or saline at 15 min and 24 h. Serum analysis of nicotinamide concentrations were conducted 1 h following the last injection. Sensorimotor and cognitive tests were conducted for 35 days following FPI. Both the 500 and 50 mg/kg doses of nicotinamide significantly facilitated recovery on the vibrissae-forelimb placing test compared to saline treatment, which showed chronic impairments. Both treatments also significantly improved performance on the bilateral tactile adhesive removal test. On the cognitive tests, the 500 mg/kg dose, but not the 50 mg/kg dose, improved performance on a working memory task in the Morris water maze (MWM). However, acquisition of a reference memory task in the MWM was not improved. Serum analysis showed that the 500 mg/kg dose significantly raised nicotinamide concentrations by 30-fold and the 50 mg/kg dose by 3-fold compared to the saline administration. This study demonstrated that raising nicotinamide concentrations resulted in the reduction of the behavioral impairments following FPI. In fact, the 500 mg/kg dose prevented the occurrence of the behavioral deficits on the bilateral tactile removal and working memory tests. Both doses significantly reduced tissue loss and glial fibrillary acid protein (GFAP) expression in the cortex. The 500 mg/kg dose reduced GFAP expression in the hippocampus. This data suggests that nicotinamide has substantial preclinical efficacy for TBI, and there appears to be some differences in the ability of the doses to improve performance in the MWM.
本研究检测了烟酰胺（维生素B3）在液体冲击伤（FPI）后以剂量依赖方式改善功能结局的能力。对受伤大鼠（平均昏迷持续时间 = 85.8秒；呼吸暂停 = 9.9秒）在伤后15分钟和24小时给予烟酰胺（500或50毫克/千克；腹腔注射）或生理盐水。在最后一次注射后1小时进行烟酰胺浓度的血清分析。在FPI后35天进行感觉运动和认知测试。与显示出慢性损伤的生理盐水处理相比，500毫克/千克和50毫克/千克剂量的烟酰胺均显著促进了触须-前肢放置试验中的恢复。两种处理还显著改善了双侧触觉黏附去除试验中的表现。在认知测试中，500毫克/千克剂量而非50毫克/千克剂量改善了莫里斯水迷宫（MWM）中工作记忆任务的表现。然而，MWM中参考记忆任务的获得并未得到改善。血清分析表明，与生理盐水给药相比，500毫克/千克剂量使烟酰胺浓度显著升高30倍，50毫克/千克剂量升高3倍。本研究表明，提高烟酰胺浓度可减少FPI后的行为损伤。事实上，500毫克/千克剂量可预防双侧触觉去除和工作记忆测试中行为缺陷的发生。两种剂量均显著减少了皮质中的组织损失和胶质纤维酸性蛋白（GFAP）表达。500毫克/千克剂量降低了海马中的GFAP表达。这些数据表明烟酰胺对创伤性脑损伤具有显著的临床前疗效，并且在改善MWM中表现的能力方面，不同剂量之间似乎存在一些差异。
