Axonal regeneration stimulated by the combination of nerve growth factor and ciliary neurotrophic factor in an end-to-side model.

The aim of this study was to investigate the potential for stimulating axonal regeneration in the context of end-to-side coaptation using a combination of nerve growth factor and ciliary neurotrophic factor in the rat sciatic nerve model. Four experimental groups (n = 8) were used: end-to-side coaptation only, end-to-side coaptation plus growth factor injection, primary repair, and nontransferred gap control. Twenty weeks after surgery histologic analysis showed that the ratio of axon density was significantly increased for the growth factor injection group. Histologic evidence suggested contamination from the proximal peroneal stump. Electrical stimulation and muscle weights showed that the target muscles had been reinnervated in all groups except the nontransferred gap control group. These data support the conclusion that the use of nerve growth factor and ciliary neurotrophic factor in combination may enhance regeneration in the peripheral nervous system. This is consistent with previous reports on the central nervous system and suggests a potential application in future studies aimed at improving peripheral nerve regeneration. Another conclusion is that contamination from the proximal peroneal stump may explain the regeneration observed in the end-to-side model. Further study using retrograde labeling is needed to establish the origin of the regenerating axons. Finally, evidence suggests that regenerating axons can use the epineurium of an intact nerve to bridge a gap in continuity.