The Effect Of Mefloquine In Pilocarpine-induced Rat Of Epilepsy

Research purpose This research established a rat epilepsy model induced by pilocarpine,and used mefloquine,a gap junction blocker,to observe its effect on the frequency of Spontaneous recurrent seizure(SRS),behavior,expressions of CCK,PV and SST inhibitory interneurons in control group,epilepsy group and mefloquine group respectively,so as to lay a foundation for further exploration of the role of gap junction in the pathogenesis of epilepsy.Methods In this study,we used pilocarpine to induce status epilepticus(SE)with chronic Spontaneous recurrent seizure(SRS)epospde model.The rats were divided into control group,epilepsy group and mefloquine group.The effects of mefloquine on spontaneous frequency,behavior and the number of inhibitory interneurons were analyzed by video recording,behavioral experiment and immunohistochemical staining respectively.Results1.The 7th day immunohistochemical staining showed that there was a signifificant reduction in the density of CCK-and SST-expressing inhibitory interneurons in epileptic rats in comparison to control rats(P < 0.05),while this reduction in the cell densities was reduced by mefloquine(P < 0.05).2.One time use of mefloquine could not reduce the frequency of spontaneous seizures in rats with temporal lobe epilepsy: compared with normal control rats,the frequency of daily episode in the epilepsy group was 7.83 ± 1.92 times / day,and that of mefloquine group was4.31 ± 1.67 times / day,there was no significant difference(P > 0.05).3.The results of open field experiment showed that there was no significant difference in the total distance of movement and the time length ratio of peripheral area / central area among the three groups.The results of new things identify experiment showed that the learning and cognitive functions of epileptic rats and mefloquine rats were damaged because they could not identify the new things which be replaced(P < 0.05).4.One month immunohistochemical staining showed that there was a signifificant reduction in the density of CCK-and SST-expressing neurons in epileptic rats in comparison to control rats(P < 0.05),and this reduction in the cell densities was not changed after treated by mefloquine(P > 0.05).Conclusion1.Acute epilepsy can lead to significant reduction in the density of CCK-and SST-expressing inhibitory interneurons in a short-period of time,and chronic spontaneous seizures can lead to a significant reduction in the density of CCK-and SST-and PV-expressing inhibitory interneurons2.After acute attack,the intervention of mefloquine can ruduce the loss of CCK-and SST-expressing inhibitory interneurons,suggesting that mefloquine may have a certain protective effect on inhibitory interneurons by blocking the gap connection.However,mefloquine intervention could not reverse the loss of inhibitory interneurons in chronic spontaneous seizures.