Department of Surgery, University of Toronto, Division of Plastic Reconstructive Surgery, 06.9706 Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Int J Mol Sci. 2020 Nov 17;21(22):8652. doi: 10.3390/ijms21228652.
Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to "find" their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.
受伤的周围神经而不是中枢神经具有再生和重新支配其靶器官的能力。在六种最严重的周围神经损伤中的两种，即挤压伤和切断伤之后，损伤部位远端的神经纤维会发生 Wallerian 变性。去神经的 Schwann 细胞 (SCs) 增殖、伸长并排列在内膜管中，以引导和支持再生轴突。轴突从与神经元体相连的存活神经的残端中出现。SCs 下调髓鞘相关基因，同时上调包括神经营养因子在内的与生长相关的基因，就像受损神经元一样。然而，基因表达是短暂的，并逐渐无法支持 SC 包含的内膜管内的轴突再生。此外，尽管一些再生的运动和感觉轴突有“寻找”其适当途径的偏好，但轴突无法进入其原始的内膜管并重新支配原始的靶器官，这是神经外科医生面临的功能恢复障碍。临床上使用的几种手术操作，包括神经和肌腱转移、在神经修复处近端短暂低频电刺激的潜力，以及局部 FK506 应用以加速轴突生长，都令人鼓舞，同时不断的研究也在阐明神经再生的分子基础。
