Protective Effect of Topiramate and Folic Acid on Mitochondrial Damage in Hippocampal Neurons during Pentylenetetrazol-Induced Kindling in Immature Rats

Objective To explore protective effect of topiramate (TPM) and folic acid (FA) on mitochondrial damage in hippocampal CA3 neurons during pentylenetetrazol- induced kindling in immature rats.Methods Pentylenetetrazol (PTZ) - induced kindling in rats was used to establish rat models of epilepsy.Forty-eight 3-week-old male Wistar rats were randomly divided into 4 groups: two therapy groups with TPM 40 mg/(kg·d) or TPM 40 mg/(kg·d) and FA 5 mg/(kg·d) administration, 2 control groups (positive control group and negative control group) with the equal amount of distilled water administration. The seizure behaviors of rats were evaluated. Two months later, the rats were killed and the brain sections were made. The mitochondrial ultrastructures of neurons in hippocampal CA3 region were observed with transmission electron microscope.Results In the positive control group, the frequency of seizure was (48.4 ± 3.7)times, while in TPM group (44.3 ± 3.1)times and in TPM and FA group(40.8 ± 3 .7)times.The differences were significant among three groups (Pa0.01). The damage degree of mitochondrial ultrastructure was (0.34±0.09),(3.76±0.28),(2.85±0.21) and (2.09±0.31)grade in negative control group,positive control group,TPM group, TPM and FA group, respectively,there were significant differences between 4 groups (Pa0.01 ).Conclusion TPM has neuro- protective effect against epilepsy-induced mitochondrial ultrastructure damage in hippocampal neurons, and FA can strengthen neuroprotective role of TPM.