Brushart T M, Gerber J, Kessens P, Chen Y G, Royall R M
The Raymond M. Curtis Hand Center, Union Memorial Hospital, Baltimore, Maryland 21218, USA.
J Neurosci. 1998 Nov 1;18(21):8674-81. doi: 10.1523/JNEUROSCI.18-21-08674.1998.
Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.
混合神经横断后再生的运动轴突优先重新支配远端肌肉分支，这一过程称为优先运动再支配（PMR）。运动轴突侧支似乎随机进入皮肤和肌肉的雪旺氏细胞管。双标记研究表明，PMR是通过修剪皮肤通路的侧支同时保留运动通路的侧支而产生的（“修剪假说”）。如果所有投射到肌肉的侧支都得以保留，那么刺激再生性芽生应通过增加在肌肉通路中至少有一个侧支的运动神经元数量来提高特异性。在当前实验中，通过在缝合前挤压修复部位近端的神经来刺激侧支芽生，这一操作还能使神经元适应并使远端通路预先变性。进行对照实验以将这些效应与侧支生成的效应区分开来。实验在大鼠股神经上进行，并通过将其终末皮肤和肌肉分支暴露于辣根过氧化物酶（HRP）或荧光金来评估。在修复部位近端进行挤压可使运动轴突侧支至少增加五倍，并显著增加正确投射的运动神经元的百分比，这与修剪假说一致。在修复前用远端挤压对神经进行预处理对特异性没有影响。使用移植模型来区分侧支生成和远端残端预先变性 的效应。先前对股神经近端进行挤压显著提高了新鲜移植再支配的特异性。因此，刺激再生性侧支芽生增加了PMR，证实了修剪假说。然而，这种效应被新鲜未挤压的近端轴突对预先变性移植的显著特异性再支配所掩盖。预先变性对特异性的这些意外效应可能涉及多种可能的机制，因其在机制和临床方面的意义而值得进一步研究。
