Effect of Low-Dose FK506 after Contralateral C7 Transfer to the Musculocutaneous Nerve: A Study in Rats

Abstract

The purpose of this study in rats was to identify whether a minimal dose of FK506 could enhance nerve regeneration along a 4-cm cross-chest saphenous nerve graft. Our center established a cross-chest nerve regeneration model previously using the contralateral C7 root transfer to the musculocutaneous nerve. Using this model, 10 adult male Sprague-Dawley rats were divided into two groups: group 1 (N = 5) consisted of animals that did not receive any further treatment, and group 2 (N = 5) consisted of animals that received a daily subcutaneous dose of 0.7 mg/kg FK506 for a period of 4 weeks. Evaluation methods of the study groups consisted of behavioral assessment, needle electromyography studies, and qualitative and quantitative morphometry. In the FK506 group, the middle of the graft and the musculocutaneous nerve contained larger axons and thicker myelin, bicep muscle weight recovered to an average of 68% of the normal (right) side, and overall behavioral results were better (P = 0.03175) than for untreated controls. Although the FK506 group achieved higher average myelinated fiber counts in all histologic sections, higher amplitude, and shorter latency results, there was no statistically significant difference between the two groups. Contralateral C7 transfer in the rat brachial plexus is a good experimental model to assess nerve regeneration and test treatments designed to enhance recovery in lesions with long nerve gaps (40 mm). FK506-treated animals demonstrated more advanced axonal regeneration, myelinated fiber maturation, and bicep muscle reinnervation. These results suggest a potential clinical use of low-dose FK506 in patients with severe nerve injuries.