Department of Clinical Neuroscience, Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Exp Neurol. 2011 Jun;229(2):460-70. doi: 10.1016/j.expneurol.2011.03.017. Epub 2011 Mar 31.
Nerve growth factor (NGF) has been previously shown to support neuron survival and direct neurite outgrowth in vitro, and to enhance axonal regeneration in vivo. However, a systematic analysis of NGF dose and dose duration on behavioral recovery following peripheral nerve injury in rodents has not been previously investigated. Here, we show that NGF promotes a bell shaped dose-response, with an optimal threshold effect occurring at 800 pg/μl. High dose NGF inhibited regeneration. However, this effect could be reversed through functional blockade of p75 receptors, thus implicating these receptors as mediators of the inhibitory response. Longer term evaluation showed that animals administered NGF at 80 ng/day for 3 weeks had greater sensorimotor recovery compared to all other treatment groups. These animals made significantly fewer errors during skilled locomotion, and displayed both increased vertical and fore-aft ground reaction forces during flat surface locomotion. Furthermore, terminal electrophysiological and myological assessments (EMG, wet gastrocnemius muscle weights) corroborated the behavioral data. Overall, these data support the hypothesis that both appropriate dose and duration of NGF are important determinants of behavioral recovery following nerve injury in the rat.
神经生长因子（NGF）先前已被证明可支持体外神经元存活和轴突生长，并增强体内轴突再生。然而，鼠外周神经损伤后，NGF 剂量和剂量持续时间对行为恢复的系统分析尚未得到研究。在这里，我们显示 NGF 促进钟形剂量反应，在 800pg/μl 时出现最佳阈值效应。高剂量 NGF 抑制再生。然而，这种效应可以通过功能性阻断 p75 受体来逆转，因此这些受体被认为是抑制反应的介导者。长期评估表明，每天给予 NGF80ng 治疗 3 周的动物与所有其他治疗组相比，有更好的感觉运动恢复。这些动物在熟练运动中犯错明显更少，在平面运动时垂直和前后地面反作用力也明显增加。此外，终端电生理和肌学评估（EMG、湿比目鱼肌重量）证实了行为数据。总的来说，这些数据支持这样一种假设，即 NGF 的适当剂量和持续时间是大鼠神经损伤后行为恢复的重要决定因素。
