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, ju st before reinnervation of the muscle occurred. Two to 4 months later the n umber of motoneurons supplying soleus, tibialis anterior, and extensor digi torum longus, muscles was established by retrograde labeling with horseradi sh peroxidase injected into the muscle. After nerve injury at 5 days there was no significant loss of motoneurons to any muscle. However, when the inj ury was repeated, the number of labeled motoneurons was reduced, suggesting that a significant proportion had died. Motoneurons to soleus were affecte d more than those to the fast muscles, reflecting their lesser maturity. Mo reover, motoneurons to soleus, that survived both injuries to their axon fa iled to grow to their full size. The relative impairment of recovery of the muscles, indicated by weight and maximal tetanic tension, mirrored the los s of motoneurons in each case. Previous studies have suggested that repeate d nerve injuries in adult animals can enhance reinnervation. However, the p resent results along with those of other recent studies suggest that immatu re 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. (C) 2001 Academic Press.