The peripheral nervous system: injury and disease

Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Whilst motoneurons and to a lesser extent, sensory neurons survive the injuries, outgrowth of axons across the injury site is slow and the neuronal regenerative capacity is progressively reduced when neurons remain without targets and chronically denervated Schwann cells fail to support axon growth. Strategies including brief low frequency electrical stimulation that accelerates axon outgrowth and, in turn, target reinnervation and functional recovery, have excellent potential for translation to human patients. Other strategies including the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete injuries. During muscle reinnervation the properties of the motoneurons and muscle fibers that they supply are rematched that provide some control of muscle force even when regenerating axons are misdirected to foreign targets. Axon sprouting from intact nerves is effective, although limited, in reinnervating denervated muscle fibers after incomplete injuries and in poliomyelitis. Studies in mouse models of amyotrophic lateral sclerosis however, indicate that sprouting is very limited with rapid and preferential loss of the largest and fastest contracting motor units during the asymptomatic phase of the disease