Pretreatment of nerve grafts with resveratrol improves axonal regeneration following replantation surgery for nerve root avulsion injury in rats

Background: Replantation of the avulsed nerve root has been proposed for the treatment of severe brachial plexus injury for several decades. However, due to the complexity of the technique and limited functional improvement, practical applications are yet to be implemented. Objective: In the present study, we investigated the effect of pretreatment with resveratrol on nerve autografts used for replantation surgery in a rat model of nerve root avulsion. Methods: Resveratrol pretreatment was performed using an explant culture technique. Two surgical procedures were performed. During the first surgery, Sprague-Dawley rats were subjected to left C6 nerve root avulsion, and nerves were harvested for autografting. The harvested grafts were explant-cultured for 1 week. A second procedure was performed to replant the C6 nerve root using the explant-cultured nerve graft 1 week after the first procedure. Histological and immunohistochemical analyses were performed 8 weeks after the second procedure. We first compared findings between explant-cultured nerve grafts and fresh nerve grafts, following which we compared findings between explant-cultured grafts pretreated with and without resveratrol. Changes induced within nerve grafts by 1 week of explant culture with or without resveratrol were investigated in vitro. Results: There was no significant difference in outcomes between 1 week-explant-cultured and fresh nerve grafts. Addition of resveratrol to the explant culture medium resulted in a significant increase in the number and myelin thickness of regenerated axons, and in the number of regenerating motor neurons in the C6 spinal cord segment. In vitro analyses revealed that nerve grafts pretreated with resveratrol exhibited significant increases in glial cell line-derived neurotrophic factor (GDNF) expression and the number of dedifferentiated Schwann cells. Conclusions: Resveratrol may promote axonal regeneration following replantation surgery for the treatment of nerve root avulsion injury; however, further studies are required to verify these findings in humans.