Repeated injury to the sciatic nerve in immature rats causes motoneuron death and impairs muscle recovery

Injury to the sciatic nerve of newborn rats causes motoneuron death, while the same insult inflicted 5 days later does not. In this study the effects of prolonging the period of target deprivation and axonal regeneration were investigated by inflicting a second nerve crush 6 days after the first, just before reinnervation of the muscle occurred. Two to 4 months later the number of motoneurons supplying soleus, tibialis anterior, and extensor digitorum longus muscles was established by retrograde labeling with horseradish peroxidase injected into the muscle. After nerve injury at 5 days there was no significant loss of motoneurons to any muscle. However, when the injury was repeated, the number of labeled motoneurons was reduced, suggesting that a significant proportion had died. Motoneurons to soleus were affected more than those to the fast muscles, reflecting their lesser maturity. Moreover, motoneurons to soleus that survived both injuries to their axon failed to grow to their full size. The relative impairment of recovery of the muscles, indicated by weight and maximal tetanic tension, mirrored the loss of motoneurons in each case. Previous studies have suggested that repeated nerve injuries in adult animals can enhance reinnervation. However, the present results along with those of other recent studies suggest that immature motoneurons that are repeatedly induced to support growth of their axons are at greater risk of death and can result in poorer reinnervation of the muscles.