Department of Orthopedics and Traumatology, University of Cologne, Joseph-Stelzmann-Strasse 9, Cologne, Germany.
Ann Anat. 2011 Jul;193(4):286-303. doi: 10.1016/j.aanat.2011.02.014. Epub 2011 Mar 12.
Insufficient recovery after peripheral nerve injury has been attributed to (i) poor pathfinding of regrowing axons, (ii) excessive collateral axonal branching at the lesion site and (iii) polyneuronal innervation of the neuromuscular junctions (NMJ). The facial nerve transection model has been used initially to measure restoration of function after varying therapies and to examine the mechanisms underlying their effects. Since it is very difficult to control the navigation of several thousand axons, efforts concentrated on collateral branching and NMJ-polyinnervation. Treatment with antibodies against trophic factors to combat branching improved the precision of reinnervation, but had no positive effects on functional recovery. This suggested that polyneuronal reinnervation--rather than collateral branching--may be the critical limiting factor. The former could be reduced by pharmacological agents known to perturb microtubule assembly and was followed by recovery of function. Because muscle polyinnervation is activity-dependent and can be manipulated, attempts to design a clinically feasible therapy were performed by electrical stimulation or by soft tissue massage. Electrical stimulation applied to the transected facial nerve or to paralysed facial muscles did not improve vibrissal motor performance and failed to diminish polyinnervation. In contrast, gentle stroking of the paralysed muscles (vibrissal, orbicularis oculi, tongue musculature) resulted in full recovery of function. This manual stimulation was also effective after hypoglossal-facial nerve suture and after interpositional nerve grafting, but not after surgical reconstruction of the median nerve. All these findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.
周围神经损伤后的恢复不足归因于 (i) 再生轴突的寻径不良，(ii) 损伤部位轴突的过度侧支分支，以及 (iii) 运动终板的多神经元支配。面神经横断模型最初用于测量不同治疗方法后的功能恢复，并研究其作用机制。由于很难控制数千个轴突的导航，因此研究集中在侧支分支和 NMJ 多神经支配上。用抗营养因子的抗体治疗来对抗分支，改善了再支配的准确性，但对功能恢复没有积极影响。这表明多神经元再支配 - 而不是侧支分支 - 可能是关键的限制因素。已知可以扰乱微管组装的药理学药物可以减少前者，并随之恢复功能。由于肌肉的多神经支配是依赖于活动的，可以进行操纵，因此尝试通过电刺激或软组织按摩来设计一种临床可行的治疗方法。应用于面神经横断或麻痹的面肌的电刺激并不能改善触须运动表现，也不能减少多神经支配。相比之下，轻柔地按摩麻痹的肌肉（触须、眼轮匝肌、舌肌）可使功能完全恢复。这种手动刺激在舌下神经-面神经缝合后和神经移植后也是有效的，但在正中神经手术重建后则无效。所有这些发现都希望能够很快设计和测试出可行且有效的临床治疗方法。
