CDP-choline and its endogenous metabolites, cytidine and choline, promote the nerve regeneration and improve the functional recovery of injured rat sciatic nerves

Objective: Topical cytidine-5'-diphosphocholine (CDP-choline) has been shown to improve the functional recovery and promote the nerve regeneration of injured sciatic nerves in rats. The aims of this study were to test whether CDP-choline was effective at promoting nerve healing when the surgery to repair an injury was delayed and to determine whether the cytidine and/or the choline moieties of CDP-choline contribute to its beneficial actions. Methods: One hundred and fifty Sprague-Dawley rats underwent a surgical procedure that involved damaging the right sciatic nerve and suturing the epineurium. The injured sciatic nerve was either repaired immediately (on the first day) or on the third day after surgery. Rats were assigned to one of five groups and received a topical application of either 0.4 ml of saline (control) or 0.4 ml of 100 mu M CDP-choline, cytidine, choline, or cytidine+choline. Results: The sciatic function index (SFI) of the rats in both groups (those who had their nerve repair immediately versus those on day 3) improved gradually by 4, 8, and 12 weeks after surgery. The percentage recovery in SFI score was significantly higher in rats treated with CDP-choline or cytidine+choline at all time points. Axon count increased by similar to 50% in rats treated either with CDPcholine or cytidine+choline. Treatment with CDP-choline or cytidine+choline reduced scar formation and decreased nerve adherence when the sciatic nerve was repaired immediately, and rats treated with CDPcholine or cytidine+choline had better axonal organization than control rats. Treatment with choline or cytidine alone led to a less marked improvement in SFI score and failed to increase axon count. Conclusion: Our results demonstrate that CDP-choline, as well as the combination of its metabolites, cytidine+choline, improves the functional recovery and promotes the regeneration of injured sciatic nerves treated with immediate or delayed surgical repair in rats.