Peripheral axon regeneration
Peripheral nerve lesions are common. They cause motor and sensory deficits with often serious clinical consequences such as prolonged paralysis, anaesthesia or neuropathic pain. Although advanced microsurgical techniques have been developed that result in minimal scar formation, the functional outcome of peripheral nerve injuries is often unsatisfactory, even after nerve repair and correct matching of nerve fascicles from the proximal and distal stump. Successful axonal regeneration through the site of injury and reconnection to the appropriate targets is rarely observed. For example, after repair of median nerve lesions full motor function is restored in less than 25% and normal sensation in less than 3% of the patients (Cooney, 1991). If the cut ends of a lesioned nerve trunk cannot be easily apposed by suture of the epineurium like in severe lacerating injuries, nerve grafts or artificial conduits are required as a bridge between the nerve ends (Archibald et al., 1995).
Improvement of long-distance axonal elongation is important for fast regeneration of axons into target muscles which atrophy in the absence of reinnervation. Apparently, the growth permissiveness of the denervated nerve decreases in a proximal-to-distal direction relative to the site of the injury resulting in the failure of regenerating axons to grow into the very distal segments of the lesioned nerve. This observation explains why the rate of recovery correlates inversely with the distance between the lesion site and the target tissue. Therefore, any therapeutic strategies should follow two main goals: 1) to increase the elongation rate of regenerating axons by stimulation of the intrinsic neuronal growth program and 2) to enhance the growth permissiveness of the denervated nerve by maintaining Schwann cell proliferation and vascular supply of the lesioned nerve.
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