Motor neuron regeneration through end-to-side repairs is a function of donor nerve axotomy

Background: Over the past decade, a growing body of literature has emerged supporting the use of end-to-side (terminolateral) neurorrhaphy for the treatment of selected peripheral nerve injuries. It remains unclear, however, whether injury to the donor nerve is necessary to achieve significant regeneration through such repairs. Methods: End-to-side repair was studied in a rodent model in which the terminal limb of a transected peroneal nerve was sutured to the lateral aspect of the tibial nerve. Twenty-eight Lewis rats were randomized to four groups of seven animals each corresponding to incrementally greater donor nerve injuries as follows: group 1, conventional end-to-side neurorrhaphy; group 2, end-to-side neurorrhaphy with proximal crush injury; group 3, end-to-side neurorrhaphy with neurotomy; and group 4, end-to-end repair of transected peroneal nerve (positive control). Results: At 12 weeks, retrograde labeling of cell bodies of the ventral hom demonstrated significant differences between experimental groups, with mean counts in group 4 (1237 +/- 171) > group 3 (522 +/- 204) > group 2 (210 +/- 132) >= group 1 (126 +/- 146). This association between nerve injury and motor neuron counts was closely mirrored in quantitative assessments of peripheral nerve regeneration and normalized wet muscle masses. Conclusions: These data support the hypothesis that donor nerve injury is a prerequisite for significant motor neuronal regeneration across end-to-side repairs. Motor neuron regeneration through end-to-side repairs is optimized by deliberate transection of donor nerve axons.