Fasudil promotes axon and myelin regeneration and functional recovery after sciatic nerve injury in rats
Objective To investigate the effect of Fasudil in improving axon and myelin regeneration and functional recovery after peripheral nerve injury.Methods Thirty SD rats weighing(200±30)g were randomly divided into two groups:control group and Fasudil group.Normal saline and 10 mg/kg hydrochloride Fasudil were intraperitoneal given,respectively.The right sciatic nerve was transected and sutured.Two weeks after operation,the density of NF-200 positive axons at the distal end of the injury was evaluated.Four weeks after operation,the number of neurons in the L4-6 dorsal root ganglia(DRG)and sacrolumbar enlargement that sent axons to the nerve distal to the transection site was evaluated by retrograde tracing using Fluoro-gold.Twelve weeks after operation,the wet weight ratio of gastrocnemius muscle and the cross-sectional area of muscle fibers were measured;and immunohistochemistry using primary NF-200 and MPZ antibodies and transmission electron microscopy were used to measure the diameter and thickness of axons and myelin sheaths.The footprints of rats at 4,6,8,10,and 12 weeks after operation were collected to evaluate the sciatic function index(SFI)of rats in the two groups.In addition,rat embryonic dorsal root ganglion(DRG)and spinal motor neurons(SMN)were cultured to evaluate the effect of Fasudil on axon growth.Results At 14 days after operation,the density of NF-200 positive axons at the distal end of the Fasudil group was significantly higher than that of control group(P=0.034).Four weeks after operation,the number of L4-6 DRG and spinal ventral horn motor neurons retrogradely labeled by Fluoro-gold in Fasudil group was significantly higher than that in control group(P＜0.05).Twelve weeks after operation,the number of myelinated axons,diameter of myelinated axons,and thickness of myelin sheaths in Fasudil group was higher than those in control group(P＜0.05),while G-ratio value was lower than that in control group(P＜0.05).The SFI data showed that at 6,8,10,and 12 weeks after operation,the SFI values in Fasudil group were significantly better than those in control group(P＜0.05).Twelve weeks after operation,the wet weight ratio of gastrocnemius muscle and cross-sectional area of myofibrils in control group were significantly smaller than those in Fasudil group(P＜0.01).After culturing for 5 days,the axons of DRG and SMN in Fasudil group were significantly longer than those in control group(P＜0.01).Conclusions Fasudil can promote axon and myelin regeneration after sciatic nerve injury in rats and improve their motor function recovery.
ROCK inhibitorsFasudilSciatic nerve injuryAxon and myelin regeneration
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