Hippocampal low-frequency stimulation increased SV2A expression and inhibited the seizure degree in pharmacoresistant amygdala-kindling epileptic rats

Abstract

To investigate the effects of hippocampal low-frequency stimulation (Hip-LFS) on the expression of synaptic vesicle protein 2A (SV2A) and on the seizure degree in pharmacoresistant epileptic rats. Eighteen pharmacoresistant epileptic rats were selected from 75 amygdala-kindling rat models of epilepsy by testing their seizure response to phenytoin (PHT) and to phenobarbital (PB). Six pharmacoresistant epileptic rats (PRE group, 6 rats) were used to determine SV2A expression for comparison with the pharmacosensitive epileptic rats (PSE group, 6 rats). The other 12 pharmacoresistant epileptic rats were assigned to a pharmacoresistant control group (PRC group, 6 rats) or to a pharmacoresistant stimulation group (PRS group, 6 rats) and were subjected to the hippocampal stimulation experiment. A stimulation electrode was implanted into the hippocampus for both the PRC group and the PRS group. Hip-LFS was administered twice per day for two weeks. Following 2 weeks of stimulation, seizure duration and frequency were observed, and SV2A mRNA expression and protein content in the hippocampus were measured by real-time PCR and by western blot analysis, respectively. The SV2A mRNA and protein decreased markedly in the PRE group compared with the PSE group. After performing Hip-LFS for two weeks, remarkable increases in SV2A mRNA and protein were observed in the PRS group compared with the PRC group (P<0.05). Simultaneously, the seizure degree of these rats was inhibited. Hip-LFS may have prevented seizures in the pharmacoresistant epileptic rats. The antiepileptic effects of Hip-LFS may be partly achieved by increasing SV2A expression.