Study On The Dose Effect Relationship Between Current Resistance And Therapeutic Effect In Conduction Treatment Of Temporal Lobe Epilepsy In Rats

ObjectiveTo investigate the effect of different current resistance on therapeutic outcome and the mechanism of current conduction treatment in rats with temporal lobe epilepsy(TLE).MethodsSprague-Dawley rats were randomly divided into control,low-resistance conduction(LRC),and high-resistance conduction(HRC)group.After the rats with TLE were established with kainic acid,a conduction electrode was placed in the CA1 area of the right hippocampus,and an EEG electrode was placed in the CA3 area of the right hippocampus.They underwent current conduction by the electrode connected to a near zero voltage power.The rats with temporal lobe epilepsy were treated with the conduction electrode for 24 hours or 7 days.Video EEG monitoring was used to record seizures and EEG discharges.The cognitive function of rats was tested with Morris water maze.The content of Glu/GABA in hippocampus was detected by neurotransmitter analyzer.The expression levels of m RNA and protein of HMGB-1,TLR-4,IL-1β and IL-1R1 in hippocampal neurons were tested with RT-PCR and Western Blot technique,respectively.The observation expression of HMGB-1/TLR-4 and IL-1β/IL-1R1 were also finished by immunohistochemistry and immunofluorescence.Results1.In the model of temporal lobe epilepsy induced by kainic acid,10~20minutes after the injection of kainic acid,the symptoms of chewing movement,behavioral dullness,body rigidity and so on began to appear,followed by unilateral or bilateral forelimb twitches,wet dog-like jitters,involuntary twitches or spasms of limbs,and finally the whole body rigidity-spasms and falls.The success rate of modeling was 85.33%,and the death rate was 7.33%.Among150 rats,128 epilepsy models were successfully established,of which 2 died within 2 hours after the injection of pentobarbital sodium,9 died within 24 hours after the seizure,and 11 did not have typical seizures.2.The total number of seizures in temporal lobe epilepsy SD rats was in LRC group than HRC group than in the epileptic control group;The total seizure frequency and transmissive seizure frequency of the LRC group were lower than those of the epileptic control group and the HRC group(P<0.01),while the total seizure frequency of the HRC group(P<0.05)and transmissive seizure frequency(P<0.01)were lower than those of the epileptic control group.The latency of the first spike in the LRC group was significantly longer than that in the epileptic control group(P<0.01).The number of platform crossings in Morris water maze space exploration test in the LRC group was significantly higher than that in the epileptic control group and the HRC group(P<0.05).3.Significant differences were found in Glu/GABA ratio at 20-180 min between epileptic control and LRC group,and at 20-120 min between HRC and LRC group.4.RT-PCR: The average m RNA level of IL-1β in LRC group(P<0.01)and HRC group(P<0.05)was significantly lower than that in the epileptic control group after 24 hours of current conduction therapy.And,the average m RNA level of IL-1β in LRC group(P<0.05)was significantly lower than that in the HRC group after 24 hours of current conduction therapy.After 7 days of current conduction therapy,The m RNA levels of HMGB-1/TLR-4 and IL-1β/IL-1R1 in LRC group(P<0.01)were significantly lower than those of the epileptic control group.The m RNA content of IL-1β(P<0.01),IL-1R1 and TLR-4(P<0.05)in HRC group was significantly lower than that in the epileptic control group.5.West blotting: At 24 h after current conduction,The content of HMGB1,TLR4,IL-1β and IL-1R1 in LRC group were significantly lower than that in the epileptic control group(P<0.01)and HRC group(P<0.05).In the 7-day subgroup of current conduction,The expression of HMGB1,TLR4,IL-1β and IL-1R1 protein was lower in LRC group than in HRC group than in the epileptic control group.6.The staining positive rate of HMGB-1/TLR-4 and IL-1β/IL-1R1 protein were observed by immunohistochemistry and immunofluorescence: LRC group< HRC group< epileptic control group.ConclusionsDifferent current resistance effected the seizure control and cognitive protection in rats with TLE treated by current conduction.Current conduction therapy is effective.The lower the resistance,the better the therapeutic effect.The Glu/GABA,and IL-1 β/IL-1R1,and TLR-4 may take part in the antiseizure mechanism of current conduction treatment.