Schwann cell dependence of regenerating rat sensory neurons is inversely related to the quality of axon growth substratum

It is still controversial to what extent elongation of regenerating sensory axons depends on proliferating Schwann cells (SCs) in an injured peripheral nerve. We hypothesized that such regeneration was independent of SC support early after nerve injury, but later became SC-dependent. The sural nerve in rats was crushed, and freezing destroyed cells but not their basal laminae (BL) in the distal nerve segment. Sensory axon elongation was assessed by the nerve pinch test and their abundance was examined immunohistochemically. Sensory axons regenerated fairly rapidly during the first week even if SC migration was prevented. Thereafter they ceased to elongate and withdrew until their terminals contacted the SCs migrating from the proximal nerve segment. Intrinsic neuronal capacity for growth without cell support, however, had not been lost. Rather, progressive degradation of the former SC BL and loss of laminin in the acellular segment arrested axon growth. Further elongation occurred only when SC migration was possible, corroborating our hypothesis. Sensory neurons continued to elongate and maintain their axons in spite of deteriorating growth substratum if, prior to injury the axons had been allowed to sprout into the denervated skin. Previous sprouting exposed the sensory neurons to high levels of NGF.