The Effects of 5-Fluorouracil applied following repair of rat sciatic nerve on epineural scar formation and nerve regeneration

SUMMARY Epineural and extraneural scarring is one of the factors negatively influencing the result of peripheral nerve surgery. Epineural scarring results in conduction block and establishes a mechanical barrier to axonal regeneration and extraneural scarring may lead to adhesions and tethering of nerves to adjacent tissues. Experimentally, numbers of pharmacologic agents have been used to reduce scar formation in peripheral nerve surgery with limited success. In this study 5-Fluorouracil (5-FU), an antimetabolite agent and potent inhibitor of the proliferation of fibroblasts was used. Clinically 5-FU have been used succesfully by ophthalmologists to prevent scar formation during glaucoma filtration surgery. Sixty Sprague-Dawley rats were divided into two groups. In each rat left sciatic nerve with tibial and peroneal components were exposed and seperated with blunt d i section. Sciatic nerve was sharply and perpendicularly transected 15 mm before bifurcation and end-to-end coaptation was done with epineural suture. In the first group (n=30) 50 mg/ml 5-FU, in the second group (n=30) saline soaked sponge applied around the repair site and surrounding tissue for 5 minutes. Each of the groups was divided into three subgroups in which rats were sacrified at 4, 8, and 12 weeks for assesments. These assesments included serial functional walking track analysis, electrophysiologic studies, muscle mass evaluation, histomorphologic evaluation and gross evaluation of scar and adhesions. Wet weight of gastrocnemius muscle and electrophysiologic studies demonstrated no significant difference between two groups. Walking track analysis indicated significantly more functional regeneration in the 5-FU group than saline group at 8, 10, and 12 weeks. Gross evaluation and histologic studies have demonstrated that 5-FU significantly reduces epineural and extraneural scar formation and adhesions without impair wound healing. Ill