Gordon T, Brushart T M, Chan K M
Division of Physical Medicine and Rehabilitation/Centre for Neuroscience, Faculty of Medicine, University of Alberta, Edmonton, Alta T6G 2S2, Canada.
Neurol Res. 2008 Dec;30(10):1012-22. doi: 10.1179/174313208X362488.
Poor functional recovery after peripheral nerve injury is generally attributed to irreversible target atrophy. In rats, we addressed the functional outcomes of prolonged neuronal separation from targets (chronic axotomy for up to 1 year) and atrophy of Schwann cells (SCs) in distal nerve stumps, and whether electrical stimulation (ES) accelerates axon regeneration. In carpal tunnel syndrome (CTS) patients with severe axon degeneration and release surgery, we asked whether ES accelerates muscle reinnervation.
Reinnervated motor unit (MUs) and regenerating neuron numbers were counted electrophysiologically and with dye-labeling after chronic axotomy, chronic SC denervation and after immediate nerve repair with and without trains of 20 Hz ES for 1 hour to 2 weeks in rats and in CTS patients.
Chronic axotomy reduced regenerative capacity to 67% and was alleviated by exogenous growth factors. Reduced regeneration to approximately 10% by SC denervation atrophy was ameliorated by forskolin and transforming growth factor-beta SC reactivation. ES (1 h) accelerated axon outgrowth across the suture site in association with elevated neuronal neurotrophic factor and receptors and in patients, promoted the full reinnervation of thenar muscles in contrast to a non-significant increase in MU numbers in the control group.
The rate limiting process of axon outgrowth, progressive deterioration of both neuronal growth capacity and SC support, but not irreversible target atrophy, account for observed poor functional recovery after nerve injury. Brief ES accelerates axon outgrowth and target muscle reinnervation in animals and humans, opening the way to future clinical application to promote functional recovery.
周围神经损伤后功能恢复不佳通常归因于不可逆的靶器官萎缩。在大鼠中，我们研究了神经元与靶器官长期分离（长达1年的慢性轴突切断术）以及远端神经残端雪旺细胞（SCs）萎缩的功能结果，以及电刺激（ES）是否能加速轴突再生。在患有严重轴突退变的腕管综合征（CTS）患者以及进行了减压手术的患者中，我们研究了ES是否能加速肌肉再支配。
在大鼠和CTS患者中，通过慢性轴突切断术、慢性SCs去神经支配后，以及在有或没有20 Hz的ES连续刺激1小时至2周的情况下立即进行神经修复后，通过电生理和染料标记来计数再支配的运动单位（MUs）和再生神经元的数量。
慢性轴突切断术使再生能力降低至67%，外源性生长因子可缓解这种情况。SCs去神经支配萎缩导致再生减少至约10%，福司可林和转化生长因子-β使SCs重新激活可改善这种情况。ES（1小时）加速了轴突穿过缝合部位的生长，同时神经元神经营养因子和受体水平升高，并且在患者中，与对照组中MUs数量无显著增加相比，ES促进了鱼际肌的完全再支配。
轴突生长的限速过程、神经元生长能力和SCs支持的逐渐恶化，而非不可逆的靶器官萎缩，是导致神经损伤后观察到的功能恢复不佳的原因。短暂的ES可加速动物和人类的轴突生长和靶肌肉再支配，为未来促进功能恢复的临床应用开辟了道路。
