The effect of aging on the morphological nerve changes during muscle reinnervation after nerve crush.

The extent of the muscle endplate reinnervation that followed crush injury of the sciatic nerve was compared between young adult (4 and 5 months old) and aged (24 months old) animals. The time course of regeneration in the muscular nerve bundle, its ramification, and the nerve terminal was immunohistochemically estimated using an antibody against the neuron specific enolase (NSE), a neuronal marker. During early phases of regeneration (7, 21 and 28 days post-crush) in the young adult animal, there were tortuosity, vacuolation and/or unfasciculation in the nerve bundle and its ramification, along with immature nerve terminals and multiple innervation. Following a subsequent advancement in reinnervation to the denervated motor endplates, the adult type of single motor innervation was common on the day 56. The old muscles basically followed the course of reversible axotomy alike the young adult ones. The age difference accounted for as follows: a reduced rate of reinnervation as indicated by a greater frequency of abnormal nerve bundles and immature nerve terminals at 28 days and 56 days post-crush, as well as unusual pathways or striking tortuosity represented by the NSE-labeled processes between day 7 and 56; late in the reinnervation period, abnormal regeneration characterized by damage of the nerve bundle, and poorly developed terminal architectures. These results suggest that despite the capability of the nerve from the old animals to extend its process, re-establishment of normal single motor innervation is reduced due to some age-related deficits, which may be related to the impaired Schwann cell-axon interactions.