American Society for Peripheral Nerve

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Axons regenerating from an intact donor nerve to a denervated recipient nerve stump through side-to-side bridges improves nerve regeneration after delayed nerve repair in Sprague- Dawley rats
Tessa Gordon, PhD; Adil Ladak; Christine A Lafontaine; Matthew D Wood; Gregory H Borschel
Hospital for Sick Children, Toronto, ON, Canada

Introduction: Poor functional recovery follows months/years for injured neurons to regenerate lost axons over long distances at 1mm/day. Our published data demonstrate that reduced regenerative capacity of the axotomized neurons without targets and reduced support of chronically-denervated Schwann cells account for this poor recovery and not inability of chronically denervated muscles to accept innervation. Here we ask whether insertion of autologous nerve bridge grafts between an intact donor nerve and a recipient denervated nerve stump 1) promote axon growth both anterograde (toward target) and retrograde (toward the soma) from a donor into a denervated distal nerve stump, 2) promote axonal growth in the stump proximal and distal to the bridges and 3) improve axon regeneration after delayed nerve repair.

Methods: Common peroneal (CP) nerve was cut and ligated and either 3 side-to-side bridges placed between donor tibial (TIB) nerve and denervated recipient CP nerve, or not. A subgroup was included in which putative muscle-derived trophic target support was removed by distal ligation of the CP nerve close to the anterior compartment muscle (LIGd). Retrogradely labeled TIB motor and sensory neurons whose axons had sprouted and/or regenerated into the denervated CP nerve stump were counted after 3m. In a second group, the proximal and distal CP nerve stumps were resutured at 4m to permit axon regeneration through the chronically denervated CP distal stump that was or was not protected by side-to-side bridges. Regenerating neurons were counted at 5m. Axon counts were made in all groups.

Results: TIB motoneurons regenerated significantly more axons antero- than retro-gradely within the chronically denervated CP stump regardless of CP nerve contact with target (mean +SE of 154±28 and 229±51 (LIGd) vs 60±23 and 66±19 (LIGd); p<0.05]. Counts were the same whether or not target connections were intact. Very few TIB motoneurons sprouted rather than regenerated their axons into the CP nerve stump. Numbers of intact TIB motoneuron declined in accord with those that regenerated their axons into the denervated CP nerve stump through the bridges. After resuture of the CP nerve stumps, the regeneration of motoneurons through the protected CP nerve stumps was significantly increased.

Conclusions: Axons regenerating across side-to-side bridges from a donor nerve into a denervated nerve stump improve regeneration after delayed surgical repair. The side-to-side technique holds promise in promoting regeneration of axons over long distances, especially as the donor axons grow both up and down the denervated distal nerve stumps. (CIHR funded)


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