Proteomics Analysis of the Regenerating Proximal Nerve After Injury and Repair: Autograft versus Nerve Lengthening

Peripheral nerve injuries are damaging nerve conditions that can result in pain and motor and sensory deficits. A number of biological processes, including structural, transcriptional, translational and growth-related pathways within nerve cells are affected by injury. In this study, we examine a peripheral nerve injury to compare protein expression level changes among control uninjured nerves and two different injury repair strategies at an early regenerative time point; such changes may be useful in predicting the eventual success of a particular repair strategy. UPLC-ESI mass spectrometry and MaxQuant LFQ and PEAKS v8.5 bioinformatic algorithms were performed on samples from the proximal stump of peripheral nerves injured and acutely repaired by autograft or a new nerve lengthening strategy, as well as uninjured contralateral control nerves. The proteins overexpressed in the lengthened sample by two-fold or greater were analyzed in DAVID, and the output data was manually clustered into 15 pathways relevant to nerve injury and regenerative processes. We present evidence of upregulated structural, immune response, bioenergetic, and protein synthesis pathways in the lengthened condition to support the stretch-activated growth hypothesis for nerves. We also highlight candidate proteins for future diagnostic or manipulation studies to characterize the nerve regeneration environment. These findings are important in advancing our understanding of the peripheral nerve regeneration process post-injury