Trophism, tropism, and specificity in nerve regeneration

Target-derived neurotrophic factors are of basic importance for survival of neurons. In the normal state, such neurotrophic factors, synthesized by the target tissues, are taken up by nerve terminals and transported by retrograde axonal transport in axons to the nerve-cell bodies to maintain their viability. After nerve injury, neurotrophic factors are synthesized by non-neuronal cells (Schwann cells and fibroblasts) in the nerve trunk, thereby supporting the outgrowth of axons. Neurite-outgrowth-promoting factors on cell surfaces (cell adhesion molecules, "recognition molecules") or in the extracellular matrix promote extension of the axons by providing an appropriate "adhesiveness" in the substrate. Both neurotrophic and neurite-outgrowth-promoting factors are essential for axonal growth after injury. Specificity in end-organ reinnervation is a complex phenomenon which may be based on physical factors at the zone of injury, as well as on molecular interaction between axons and substrate cells along the pathways and at the target level. Such processes may include molecular recognition of appropriate axons and maintenance of such axons by trophic mechanisms, as well as the pruning of inappropriate axons. The ultimate errors in target reinnervation are reflected in a cortical re-organization in the somatosensory cortex. The capacity of the brain to "reprogram" itself and adapt to this functional re-organization is critical for the ultimate recovery of functional sensory/motor function after nerve injuries.