Neuroregenerative effects of polyethylene glycol and FK-506 in a rat model of sciatic nerve injury

Abstract

The recently introduced polyethylene glycol (PEG) treatment restores axonal continuity after nerve injury, leading to rapid recovery of nerve function. The impact of PEG therapy on neuroregeneration has not yet been compared with any intervention with an established proneuroregenerative potential. FK-506 is an immunosuppressive agent with documented proneuroregenerative potential in nerve injury models. The aim of this study was to compare the effects of PEG therapy and preinjury FK-506 administration in rats with sciatic nerve transection injury. Four groups of male Sprague Dawley rats (seven per group) underwent sciatic nerve transection with primary repair. Group A received placebo injections, group B placebo injections and PEG treatment, group C FK-506 injections, and group D both FK-506 injections and PEG treatment. Clinical outcomes were assessed by the skin prick test and Sciatic Functional Index (SFI). Regenerated nerves underwent histomorphometric analysis. The histomorphometric analysis demonstrated that compared with the controls, nerve specimens from all treated groups showed signs of enhanced neuroregeneration (higher mean axonal area) (p<0.001). The histomorphometric parameters for group D (PEG + FK-506), mean axonal area (p<0.001) and axonal count (p>0.05), were significantly better than those in the other study groups. The Form factor was closest to its optimal values in group B (p<0.0001). At the end of the study, mean skin prick test scores in all treated groups were significantly higher than those in controls (p>0.05). During the first postoperative week, PEG-treated rats (groups B and D) presented with higher values of the SFI than animals from groups A and C, but the difference was not statistically significant. Combined therapy with PEG and FK-506 seems to produce better neuroregeneration outcomes than a simple suture-based repair complemented with either PEG or FK-506 treatment.