Intraperitoneal administration of CDP-choline or a combination of cytidine plus choline improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury

Abstract

Objective: Topical cytidine-5'-diphosphocholine (CDP-choline) improves functional recovery and promotes nerve regeneration in sciatic nerve injury in rats. The aims of this study were to test whether systemic treatment with CDP-choline was effective in improving the recovery of injured sciatic nerve, and to determine whether the cytidine and/or choline moieties of CDP-choline contribute to its beneficial actions. Methods: Seventy Sprague-Dawley rats underwent a surgical procedure that involved transectioning and immediate surgical repairing of the right sciatic nerve. Rats were assigned to one of five groups and administered intraperitoneally 1 ml/kg of saline ( control) or saline containing 600 mmol/kg of each of CDPcholine, cytidine, choline, or cytidine + choline. Results: Recovery in sciatic function index score was greater in rats treated with CDP-choline, choline, or cytidine + choline at 8 and 12 weeks after the interventions. Peripheral nerve regeneration evaluated by electromyography at 12 weeks was also greater in rats receiving CDP-choline ( 228% of control), choline ( 168% of control), or cytidine + choline ( 221% of control). Axon counts and axon density increased significantly following CDP-choline, choline, or cytidine + choline, respectively. Treatment with equivalent dose of cytidine failed to affect sciatic function index, electromyography, and axon counts. Treatment with CDP-choline, but not its metabolites improved nerve adherence and separability score. Conclusion: These data show that intraperitoneal CDP-choline, as well as the combination of its metabolites, cytidine + choline, improves functional recovery and promotes regeneration of injured sciatic nerves in rats. CDP-choline also improves nerve adherence and separability.