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Developing a large-gap peripheral nerve defect model in the Rhesus macaque

Sivak WN, Bliley JM, Minteer DM, McLaughlin MM, Washington KM, Spiess AM, Crammond DJ, Rubin JP, Marra KG
University of Pittsburgh
2013-03-14

Presenter: Wesley Sivak

Affidavit:
This work represents substantial effort on the part of the resident presenter.

Director Name: Joseph E Losee, MD

Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Hand

Purpose: Rodents, when utilized to assess nerve repair, are criticized for accelerated regeneration and small size; promising therapies require rigorous evaluation. This study identifies elements in a Rhesus macaque nerve model, providing an interim analysis of the first two non-human primates.

Methods: Two 2-year Rhesus macaque males were trained to retrieve from a Klüver board by right thumb-forefinger pinch. A right 5-cm median nerve gap was repaired with autograft or decellularized human nerve allograft. Nerve conduction velocity (NCV) was obtained before and after repair. Somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (Tc-MEP) were obtained pre-/post-op. Klüver board tests resumed on post-op day 13. Grafts were explanted at 90 days, obtaining NCVs prior to harvest, and analyzed for morphometry and Schwann cell density.

Results: Following injury, thumb opposition was lost and correct pinch was utilized 10-30% of the time; baseline pinch was observed at POD 87. Higher stimulation thresholds for SSEP and Tc-MEP without increased latency were seen at 37 days, returning to baseline by 90 days. NCV was 40% of baseline at explant. S-100 staining indicated similar Schwann cells density in the autograft and allograft; Masson's trichrome staining revealed normal nerve architecture.

Conclusion: Nerve regeneration in the Rhesus macaques proceeds at a rate of 1.35 mm/day, comparable to humans. More frequent electrophysiology, improved functional measurements, and exhaustive histologic methods will be required for greater insight into peripheral nerve regeneration, enabling pre-clinical evaluation of repair strategies in the model.

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