The Effects of folic acid and topiramate on peripheral nerve regeneration

Abstract

Peripheral nerve injury creates unusual sensitivity and pathological spontaneous activity in neurons that are described as ectopic discharge. Voltage dependent Na channels are responsible for ectopic discharge. Topiramate (TOP) inhibits voltage-gated sodium channels by blocking both the amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor and folic acid (FA) activity in neurotransmitter synthesis reactions. FA and TOP are anti-apoptotic agents by both phosphorylated-Akt (p-Akt) signaling activation and anti-inflammatory effects at the injury site. We investigated the effects of FA and TOP in peripheral nerve injury. We used rats with a sciatic nerve injury (SNI) treated with FA or TOP once daily for 6 weeks. Histological and electrophysiological tests were used to evaluate the morphology, and motor and sensory functions. Numbers of axons, myelin sheath thickness and axon area were measured using stereological techniques; functionality also was evaluated. Although FA exhibited a positive effect on regeneration by increasing the number of axons, we found no difference in axonal outgrowth or myelin sheath formation between the TOP and FA groups.