Decreased expression ofγ-aminobutyric acid receptor in the hippocampal tissues of pharmacoresistant temporal lobe epileptic rats

Abstract

Objective To establish a multi-drug resistant model of temporal lobe epilepsy，and to observe the changes of γ-aminobutyric acid (GABA) receptor expression in the hippocampal tissues so as to explore its effects in pharmacoresistant epileptogenesis. Methods One hundred rats were selected to prepare the amygdaloid kindled model of epilepsy by chronic stimulation of amygaloid basal ateral nucleus.After the kindled model of epilepsy was prepared successfully (n=52)，pharmacoresistant epileptic rats were selected according to their response to the phenobabital and phenytoin.The selected pharmacoresistant epileptic rats (n=8) were sacrificed and the hippocampus was removed to determine the GABA receptor expression，and the same number of pharmacosensitive epileptic rats was used as control. Results The pharmacoresistant epileptic rats displayed degenerative and necrotic hippocampal neurons.The arrangement of hippocampal neurons was disordered，and the structural characteristics of the arrangement of the hippocampal neurons disappeared.The gray values of GABAA-positive neurons in the hippocampal tissues (141.15±14.72) increased significantly compared with the pharmacosensitive epileptic rats (92.56±5.17; t=3.380，P=0.006).Western blot method demonstrated that the band of GABAA became narrowed and thin.The relative quantity of GABAA in the hippocampal tissues (0.38±0.08) decreased significantly as compared with the pharmacosensitive epileptic rats (0.88±0.18).A significant difference was observed (t=5.420，P=0.002). Conclusions GABA receptor expression might be decreased in the hippocampal tissues of pharmacoresistant epileptic rats.It might play a certain role in the formation of pharnmacoresistant epilepsy. Key words: Epilepsy，temporal lobe; Drug resistance，multiple; Kindling，neurologic; Hippocampus; Receptors，GABA; Disease models，animal