Ahlborn Peter, Schachner Melitta, Irintchev Andrey
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Falkenried 94, D-20251 Hamburg, Germany.
Exp Neurol. 2007 Nov;208(1):137-44. doi: 10.1016/j.expneurol.2007.08.005. Epub 2007 Aug 23.
The clinical outcome of peripheral nerve injuries requiring surgical repair is usually poor and efficient therapies do not exist. Recent work has suggested that low-frequency electrical stimulation of the severed nerve which produces repeated discharges of the parent motoneuron perikarya positively influences axonal regeneration, even if applied once for a period of only 1 h. Here we provide the first evidence for locomotor functional benefits of such stimulation. We transected the femoral nerve of adult C57BL/6J mice proximal to the bifurcation of the quadriceps and saphenous branches and electrically stimulated the proximal nerve stump for 1 h at 20-Hz frequency prior to nerve repair with a silicone cuff. Three months later, the ability of the quadriceps muscle to extend the knee in sham-stimulated mice had recovered to 63% of the preoperative values as estimated by single-frame motion analysis. After electrical stimulation, the outcome was only slightly better (73%) but the rate of functional recovery was considerably accelerated. Near-maximum recovery was achieved 6 weeks earlier than in the control group. The beneficial effects were associated with larger motoneuron cell bodies and increased diameters of regenerated axons in the quadriceps nerve branch, but not with enhanced preferential reinnervation by motoneurons of muscle as opposed to skin. The observed acceleration of functional restoration and the positive effects on motoneurons and regenerated axons indicate the potential of a clinically feasible approach for improvement of nerve repair outcome in human patients in which delayed target reinnervation is a factor limiting recovery.
需要手术修复的周围神经损伤的临床结果通常较差,且不存在有效的治疗方法。最近的研究表明,对离断神经进行低频电刺激,使运动神经元胞体产生重复放电,即使仅施加一次,持续1小时,也能对轴突再生产生积极影响。在此,我们首次提供了这种刺激对运动功能有益的证据。我们在成年C57BL/6J小鼠的股神经在股四头肌和隐神经分支分叉近端处进行横断,并在使用硅胶套管进行神经修复之前,以20赫兹的频率对近端神经残端进行1小时的电刺激。三个月后,通过单帧运动分析估计,假刺激小鼠的股四头肌伸展膝关节的能力恢复到术前值的63%。电刺激后,结果仅略好一些(73%),但功能恢复速度明显加快。与对照组相比,在早6周时就实现了接近最大程度的恢复。这些有益效果与股四头肌神经分支中更大的运动神经元细胞体和再生轴突直径增加有关,但与运动神经元对肌肉而非皮肤的优先再支配增强无关所观察到的功能恢复加速以及对运动神经元和再生轴突的积极影响表明,对于人类患者中延迟的靶标再支配是限制恢复的一个因素的情况,一种临床可行的改善神经修复结果的方法具有潜力。