Gordon Tessa, Sulaiman Olewale A R, Ladak Adil
Division of Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Int Rev Neurobiol. 2009;87:433-44. doi: 10.1016/S0074-7742(09)87024-4.
While injured neurons regenerate their axons in the peripheral nervous system, it is well recognized that functional recovery is frequently poor. Animal experiments in which injured motoneurons remain without peripheral targets (chronic axotomy) and Schwann cells in distal nerve stumps remain without innervation (chronic denervation) revealed that it is the duration of chronic axotomy and Schwann cell denervation that accounts for this poor functional recovery and not irreversible muscle atrophy that has been so commonly thought to be the reason. More recently, we demonstrated that axon outgrowth across lesion sites is a major contributing factor to the long delays incurred between the injury and the reinnervation of denervated targets. In the rat, a period of 1 month transpires before all motoneurons regenerate their axons across a lesion site. We have developed a technique of 1 h low-frequency electrical stimulation (ES) of the proximal nerve stump just after surgical repair of a transected peripheral nerve that greatly accelerates axon outgrowth. This technique has been applied in patients after carpal tunnel release surgery where the ES promoted the regeneration of all median nerves to reinnervate thenar muscles within 6-8 months, which contrasted with failure of any injured nerves to reinnervate muscles in the same time frame without ES. These findings are very promising such that the ES method could become a clinically viable tool for accelerating axon regeneration and muscle reinnervation.
虽然受损神经元在外周神经系统中能够再生其轴突,但人们普遍认识到功能恢复往往不佳。在动物实验中,受损的运动神经元失去外周靶点(慢性轴突切断术),远端神经残端的施万细胞失去神经支配(慢性去神经支配),结果显示,导致这种功能恢复不佳的原因是慢性轴突切断术和施万细胞去神经支配的持续时间,而非一直以来普遍认为的不可逆肌肉萎缩。最近,我们证明轴突跨越损伤部位的生长是损伤与失神经支配靶点重新获得神经支配之间出现长时间延迟的一个主要因素。在大鼠中,所有运动神经元的轴突跨越损伤部位再生之前需要经过1个月的时间。我们开发了一种技术,在切断的外周神经手术修复后,对近端神经残端进行1小时的低频电刺激(ES),这能极大地加速轴突生长。该技术已应用于腕管松解术后的患者,电刺激促使所有正中神经在6 - 8个月内再生并重新支配鱼际肌,而在相同时间范围内,没有电刺激时,任何受损神经都无法重新支配肌肉。这些发现非常有前景,电刺激方法可能会成为临床上加速轴突再生和肌肉重新获得神经支配的可行工具。