A Nonhuman Primate Model to Evaluate Treatments for Long-Gap Ulnar Nerve Injury

Abstract

Among all upper extremity nerves, the ulnar nerve is both the most commonly injured and notoriously difficult to regenerate. Despite this, ulnar nerve injuries remain understudied. Nonhuman primates (NHPs) offer an ideal model for the human upper extremity, but existing NHP nerve trauma literature is biased towards median and radial injury models. To address this, a nonhuman primate ulnar nerve injury model was developed and regeneration assessed following sural nerve autografting using electrophysiological and histological techniques. Unilateral 4 cm ulnar nerve injuries were created at the mid-forearm level, sural nerve autografts were sutured into resulting defects (n = 3), and animals were survived for 6 months. At the terminal time point, intraoperative electrophysiological testing, tissue harvest, and tissue processing were performed. Naïve nerves (n = 5) served as controls. Animals appeared clinically normal throughout the study period, other than an expected decrease in fine hand muscle function. After 6 months, histological and electrophysiological evidence suggested that axons crossed the graft and reached distal muscle targets. However, regenerating nerves exhibited a reduced motor nerve conduction velocity, reduced compound action muscle potential (CMAP) amplitude and area under the curve, increased latency, and increased duration versus naïve controls as expected. Histological analysis revealed reduced axon diameters, thinner myelin sheaths, and smaller muscle fiber cross-sectional areas as compared to controls. At 6 months post-injury, 4 cm ulnar defects bridged with sural autografts show signs of ongoing regeneration and nascent reinnervation. Specific electrophysiological and histological benchmarks for ulnar nerve recovery following clinically relevant autografting are presented.