CONTRIBUTING FACTORS TO POOR FUNCTIONAL RECOVERY AFTER DELAYED NERVE REPAIR - PROLONGED DENERVATION

The effects of prolonged denervation, independent from those of prolon ged axotomy, on the recovery of muscle function were examined in a ner ve cross-anastomosis paradigm. The tibialis anterior muscle was denerv ated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Ner ve regeneration and muscle reinnervation were quantified by means of e lectrophysiological and histochemical methods, Progressively fewer axo ns reinnervated the muscle with prolonged denervation; for example, be yond 6 months the mean (+/-SE) motor unit number was 15 +/- 4, which w as far fewer than that after immediate nerve suture (137 +/- 21), The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because eac h regenerated axon reinnervated three- to fivefold more muscle fibers than normal, Rather, it is due to progressive deterioration of the int ramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheat hs. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force, Reinnervated muscle fibers failed to fully r ecover from denervation atrophy: muscle fiber cross-sectional area bei ng 1171 +/- 84 mu m(2) as compared to 2700 +/- 47 mu m(2) after immedi ate nerve suture, Thus, the primary cause of the poor recovery after l ong-term denervation is a profound reduction in the number of axons th at successfully regenerate through the deteriorating intramuscular ner ve sheaths, Muscle force capacity is further compromised by the incomp lete recovery of muscle fibers from denervation atrophy.