Abstract
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.
Highlights
Injured nerves in the peripheral nervous system, including motor and sensory nerves supplying muscles and sense organs respectively, have the capacity to regenerate and reinnervate their target organs, unlike the nerves in the central nervous system that do not [1,2,3,4,5,6].1.1
These findings demonstrate the many levels of misdirection of regenerating motor fibers with evidence of (1) regenerating fibers randomly entering vacant endoneurial tubes at the site of nerve repair after transection injuries and the consequent misdirection of the fibers to different denervated muscles, even to physiologically antagonist muscles, (2) motor and sensory neurons regenerating their axons into inappropriate channels initially prior to channeling their axons appropriately once neurotrophic factors are differentially expressed by Schwann cells (SCs) in the sensory and motor endoneurial tubes, and (3) regenerating motor fibers branching within the intramuscular sheaths but “missing” branch points of the sheaths and reinnervating muscle fibers that they did not supply previously
Obstacles to the recovery of function after peripheral nerve injuries remain. This is despite the considerable and impressive plasticity of the neuromuscular system that observes many of the normal principles of nerve–muscle interactions during nerve regeneration and muscle reinnervation
Summary
Injured nerves in the peripheral nervous system, including motor and sensory nerves supplying muscles and sense organs respectively, have the capacity to regenerate and reinnervate their target organs, unlike the nerves in the central nervous system that do not [1,2,3,4,5,6]
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