Further Studies on Motor and Sensory Nerve Regeneration in Mice With Delayed Wallerian Degeneration

The axons of both peripheral and central neurons in C57BL/Wld(s) (C57BL/Ola) mice are unique among mammals in degenerating extremely slowly after axotomy. Motor and sensory axons attempting to regenerate are thus confronted with an intact distal nerve stump rather than axon- and myelin-free Schwann cell-filled endoneurial tubes. Surprisingly, however, motor axons in the sciatic nerve innervating the soleus muscle regenerate rapidly , and there is evidence that they may use Schwann cells associated with unmyelinated fibres as a pathway. If this is so, motor axon regeneration might be impaired in C57BL/Wld(s) mice in the phrenic nerve, which has very few unmyelinated fibres. We found that as long as the myelinated axons in the distal stump of the phrenic nerve remained intact (up to 10 days), regeneration of motor axons did not occur, in spite of vigorous production of sprouts at the crush site. In contrast to motor axons, myelinated sensory axons regenerate very poorly in C57BL/Wld(s) mice, even in the presence of unmyelinated axons. We showed that this was also due to adverse local conditions confronting nerve sprouts, for the dorsal root ganglion cell bodies responded normally to injury with a rapid induction of Jun protein-like immunoreactivity and when the saphenous nerve was forced to degenerate more rapidly by multiple crush lesions sensory axons regrew much more successfully. The findings show that motor and sensory axons in C57BL/Wld(s) mice, although very atypical in the way that they degenerate, are able to regenerate normally but only in an appropriate environment. The results also give support to the view that intact peripheral nerves either fail to encourage or actively inhibit axon growth, and that an unsuitable local environment can prevent regeneration even if the cell body is reacting normally to injury.