Donor nerve axotomy and axonal regeneration after end-to-side neurorrhaphy in a rodent model

OBJECTIVE In this study, the authors used a surgical model of end-to-side neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to investigate the optimal conditions for axonal regeneration induced by the donor nerve. They also assessed the importance of a more favorable pathway using a predegenerated nerve graft to attract regenerating axons to regrow into the graft and then directing and improving their growth toward the target in comparison with results obtained with a fresh nerve graft. METHODS End-to-side neurorrhaphy was performed between a nerve graft and a donor tibial nerve. The nerve graft was obtained from the left tibial nerve, which was either freshly removed or predegenerated 1 week prior to neurorrhaphy. The donor right tibial nerve was injured by epineurium removal alone, injured by epineurium removal with cross section of 20% or 50% of the total axons at the coaptation site, or left intact. The animals were followed postoperatively for a 6-week period, and outcomes were evaluated by optical microscopy and retrograde labeling to detect the regenerated primary sensory neurons located in the lumbar dorsal root ganglia and spinal motor neurons located in the lumbar spinal ventral horn. RESULTS At the end of the follow-up period, no regenerating axons were observed in the nerve grafts when the donor nerve was left intact, and very few axons were detected when the donor nerve was injured by epineurium removal alone. However, numerous regenerating axons appeared in the grafts when the donor nerve was axotomized, and the greatest number was achieved with a 50% cross section axotomized nerve. In the rats with a 50% cross section of the donor nerve, better nerve-like morphology of the grafts was observed, without connective adhesions. When a predegenerated nerve graft was used, more regenerating axons were attracted and elongated with a more regular shape and improved myelination. CONCLUSIONS Axonal regrowth into a nerve graft depends on axotomy of the donor nerve after end-to-side neurorrhaphy. More efficient attraction and an improved structure of the regenerating axons were achieved when a predegenerated nerve graft was used. Furthermore, a nerve graft may require a certain number of regenerating axons to maintain a nerve-like morphology.