This study investigated the therapeutic effect of hippocampal low-frequency stimulation (Hip-LFS) and its influence on the type A γ-aminobutyric acid receptor α1 subunit (GABA R α1 subunit), inducible cAMP early repressor (ICER) and brain-derived neurotrophic factors (BNDF). The model of epilepsy was induced by chronic electrical stimulation in amygdala. Drug-resistant and drug-sensitive epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital. The changes of GABA R α1 subunit, ICER and BDNF expression were detected via immunohistochemistry and western blot. The expression levels of ICER and BDNF were increased remarkably but the GABA R α1 subunit decreased significantly in the drug-resistant epileptic rats. However, the expression levels of ICER, BDNF were decreased and the expression of the GABA R α1 subunit increased significantly in the drug-resistant epileptic rats after two weeks of Hip-LFS. Meanwhile, the seizure degree was reduced and the electroencephalograms were improved. The present study demonstrated thatincreased ICER and BDNF might be associated with the development of drug-resistance. The effect of Hip-LFS in the treatment of drug-resistant epileptic rats might be associated with increasing the levels of the ICER and the BDNF.
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