American Society for Peripheral Nerve

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Side-to-side Bridging from a Donor Nerve into a Denervated Nerve Stump Improves Peripheral Nerve Regeneration after Delayed Repair in Sprague Dawley Rats
Tessa Gordon, PhD1, Adil Ladak, MD, MSc2, CA Lafontaine CA, MSc1, Jennifer Zhang, MSc1, Edward Liu1 and Gregory H. Borschel, MD, FACS, FAPP3
1Division of Plastic Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada, 2Department of Neurological Surgery, Mayo Clinic, Rochester, MN, 3Division of Plastic Reconstructive Surgery, Department of Surgery, Mayo Clinic, Toronto, ON, Canada

Background: Slow rates of regeneration of 1-3mm/day and periods of a month for regenerating axons to cross-coaptation sites result in long periods for axons to regenerate and reinnervate distant targets. Our animal studies demonstrated that neurons progressively lose their regenerative capacity with time and denervated Schwann cells (SCs) lose their ability to support regenerating axons, reducing regenerative capacity to <5-10%. Strategies must be pursued to promote axon regeneration under these unfavorable conditions. Research question: Can we 'protect' Schwann cells (SCs) and, in turn, improve nerve regeneration through chronically denervated nerve stumps? Methods: 1) Autologous common peroneal (CP) grafts, 1-9 in number and 3.2mm in length, were secured between intact donor tibial (TIB) nerve and denervated distal CP nerve stump. One to three bridges were placed between epineural windows in the TIB and CP nerves; the epineurium was cut longitudinally for >3 bridges. In the control groups, bridges were not placed. Retrograde dyes were applied to either side of a 10mm "protected zone" of the CP stump 3m later to count TIB neurons that sent axons into CP nerve. 2) CP nerve regeneration and ankle dorsiflexor muscle reinnervation were examined 5m after surgical repair of CP proximal and "protected" (experimental) or "non-protected" (control) distal nerve stumps. Results: Donor TIB axons crossed one placed bridge in only 10% of rats. Axons crossed all bridges in all the rats when ≥3 bridges were placed, growing equally in both retrograde and anterograde directions within the recipient CP nerve stump. Only few neurons sent axons in both directions. Twenty five to 35% of the neurons regenerated their axons through three bridges to occupy and become myelinated within denervated CP endoneurial tubes. Numbers of regenerating neurons and axons declined when >3 bridges were placed through the stripped epineurium and many regenerated axons grew outside of the endoneurial tubes. In the second experiment, CP nerve regeneration and numbers of CP neurons that reinnervated ankle flexor muscles were significantly higher than when CP neurons regenerated through unprotected chronically denervated CP nerve stumps. Failure of >3 bridges to promote regeneration concurred with the decreased occupancy of denervated endoneurial tubes by donor TIB nerves. Significance: Clinically, multiple small grafts from the donor nerve to the injured nerve could be used to protect proximally-injured nerves. For example, a high ulnar nerve injury could be distally protected with multiple sural nerve autografts carrying axons from the median nerve to the ulnar nerve.


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