Doxorubicin for prevention of epineurial fibrosis in a rat sciatic nerve model: outcome based on gross postsurgical, histopathological, and ultrastructural findings

Abstract

ObjectEpineural fibrosis may complicate peripheral nerve surgeries and currently is considered as one of the main factors responsible for failed surgeries. The authors investigated the postoperative antiscarring effects of topically applied doxorubicin (DXR) on rat sciatic nerves.MethodsThe sciatic nerves were dissected from the surrounding tissue and exposed bilaterally in 20 Wistar albino adult male rats. Abrasion trauma was produced on the exposed surface of the biceps femoris muscle in the vicinity of the sciatic nerves and their main branches in all animals. In the DXR Group, cottonoid pads soaked with DXR (0.5 mg/ml) were placed around the nerves for 5 minutes, whereas cotton pads soaked with saline (0.9% NaCl) were applied to nerves of animals in the Control Group for the same duration. Twelve weeks after the procedure, all of the rats were killed and the sciatic nerves were examined. Epineural adhesions were evaluated histopathologically and ultrastructurally. Additionally, quantitative histological parameters, the scar tissue formation index and the scar density, were calculated in histological evaluation.ResultsGross postsurgical evaluation as well as histopathological and electron microscopic examination of involved nerve segments showed significantly less epineurial adhesions in the DXR Group than in the Control Group. Quantitative analysis of the epineurium revealed a statistically significant reduction in the density and amount of epineural scarring in specimens from the DXR Group than in those from the Control Group.ConlusionsThe results of gross postsurgical anatomical evaluation and histopathological and ultrastructural studies suggested that topical application of DXR effectively reduced epineural scar formation on rat sciatic nerves. These promising findings merit further experimental and clinical studies to determine the efficacy and safe applicability of DXR in human subjects.