American Society for Peripheral Nerve

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Motor and Sensory Donor Axons Growing Across Two End-to-side Neurorrhaphies Through an Autograft ‘Protect' Chronically Denervated Schwann Cells to Improve Nerve Regeneration After Delayed Nerve Repair in Rats
Tessa Gordon, MD; Jennifer J. Zhang, MD; Gregory H. Borschel, MD
Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, ON, Canada

Introduction: End-to side neurorrhaphy where a transected nerve is repaired to the side of an intact nerve may circumvent long delays for nerve regeneration through long autografts or artificial conduits1. Side-to-side bridging with two end-to-side neurorrhaphies is another option when only the distal stump is available2. The relative contributions of motor and sensory axons growing into the recipient denervated distal nerve stump have not yet been determined. Mackinnon’s group reported that very few motoneurons regenerated axons through an end-to-side neurorrhaphy3. We asked the questions: 1) How many motor and sensory neurons send their axons through autologous side-to-side bridges between an intact donor nerve and an adjacent chronically denervated nerve stump? 2) Do these donor nerves alleviate the negative effects of chronic Schwann cell denervation by promoting effective nerve regeneration and, in turn, target reinnervation?

Methods: 1) Common peroneal (CP) autografts were secured with Tisseel glue between 10mm lengths of a donor tibial nerve and a recipient CP distal nerve stump, three between epineurial windows and 5-9 bridges after removing the epineurium. Retrograde dyes were applied ~6mm proximal and distal to the bridges for enumeration of sensory and motor neurons that grew axons into the 3 month chronically denervated CP nerve stump. 2) Transected CP nerve stumps were opposed for surgical repair. Motor and sensory neurons that had regenerated their axons after 5 months were enumerated and isometric force recordings were made to count the motor nerves that reinnervated muscle.

Results: 1) Motor and sensory neurons regenerated axons in equal numbers from a donor tibial nerve across 1-9 bridges both proximal and distal to the bridges in the recipient chronically denervated CP nerve stump. 2) Three but not more bridges significantly increased regeneration of motor and sensory CP nerves after delayed CP nerve coaptation. The numbers of CP motoneurons that regenerated their axons increased 3-fold and fully reinnervated flexor muscles with complete recovery of their mass.

Conclusions: Both motor and sensory nerves grow through bridges toward recipient denervated nerve stumps. They effectively ‘protect’ chronically denervated Schwann cells to significantly improve sensory regeneration and promote regeneration and muscle reinnervation of all motoneurons. Partial occupancy of chronically denervated nerve stumps with donor axons promotes a growth permissive state, possibly via neuregulin signaling.
1. Ray WZ, Mackinnon SE (2010) Exp Neurol 223:77-85.
2. Viterbo F et al (1994) Br J Plast Surg 47:75-80.
3.Tarasidis G et al (1997) Ann Otol Rhinol Laryngol 106:506-512.

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