Investigation of the effectiveness of uridine treatment on nerve regeneration and scar tissue formation in experimental sciatice nerve damage model

Peripheral nerve regeneration is still unsolved problem in regenerative medicine. Uridine as bloodstream major pyrimidine nucleoside is a precursor of membrane phospholipid synthesis via the Kennedy pathway. Our purpose is investigation the effect of systemic uridine administration.after unilateral sciatic nerve injury on regeneration and scar tissue formation. In this study, 96 adult male Sprague Dawley rats were used. They were divided into two main groups as early (4 groups) and late (4 groups). Right sciatic nerve transection and suturing were performed in all groups except first one. Intraperitoneally once a day for a week, saline in the first and second groups (Sham and Control), Uridin 100mg/kg (U100) in the third, Uridine 500mg/kg (U500) in the fourth groups, had been injected. Early groups were sacrificed at the 1st and late at the 12th week. In early groups, apoptotic marker, oxidation damage and antioxidative defense mechanisms were examined. In the late ones, after the sciatic functional (SFI) and electrophysiological (EMG) tests, the sciatic nerves were removed and axon healing was examined. Anti-apoptosis effect was found to be significant in U500 rats compared to control (p <0.05). In the U100 and U500 groups, oxidation parameters decreased significantly compared to control (p <0.001) and anti-oxidation parameters increased (p <0.001). In the U500 group, significantly better results were found in terms of nerve separability than control (p=0.002). In the 6th and 12th week SFI U100 and U500 groups showed significant improvement compared to control (p <0.001). At 12th week EMG analysis showed high amplitude values in U500 group compared to control and U100 (p<0.001). In terms of the number of myelinated axons; statistically increase observed in U100 and U500 groups compared to control (p <0.05). Systemically Uridine administeration has anti-apoptotic and anti-oxidative effects, especially in a dose-dependent manner. In addition, SFI improvement, nerve tissue regeneration, perineural scar tissue decrease, shortening of EMG latency, nerve seperability score improvement and myelinated axones increase were observed.