Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy

Objective To study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy. Methods Rat models of epilepsy were prepared by pentylenetetrazol (PTZ)-induced kindling. Seventy-two 3-week-old male Wistar rats were randomly divided into 6 groups: four TPM-treated epilepsy groups ( TPM 20, 40 or 80 mg/kg·d and TPM 40 mg/kg·d + FA 5 mg/kg·d), a positive control group (untreated epilepsy group) and a negative control group (normal control group). After two months of administration, behaviors of the rats were recorded; serum levels of neuron-specific enolase (NSE) were measured using ELISA; pathological changes in the hippocampus were observed.Results The frequency of convulsion seizures in the 20, 40 and 80 mg TPM treatment and TPM+FA groups was 44.7 ±2.9, 44.3±3.1, 42.7±3.2, and 40.8±3.7 respectively, which were significantly lower than that in the positive control group (48.4±3.7) (P0.01). Twenty, forty and eighty mg TPM treatment and TPM+FA treatment significantly reduced NSE levels from 35.71±5.97 μg/L of the control group to 27.40±6.40, 24.79±6.22, 21.47±6.87 and 22.55±7.02 μg/L respectively (P0.05). Neuronal apoptosis in the CA3 and CA1 regions were alleviated in the four TPM-treatment groups compared with positive control. The number of necrotic neurons was progressively reduced with the increased dose of TPM. The 40 mg TPM+FA treatment group showed less necrotic neurons in the CA3 and CA1 regions than the 40 mg TPM alone treatment group.Conclusions TPM has protective effects against epilepsy-induced neuronal damage. The effect is dose-dependent. A combination of TPM and FA can produce a synergistic effect.