Chronic Vagus Nerve Stimulation Alters The Levels Of Some Cytokines In The Hippocampus Of Rats With Lithium-Pilocarpine Epilepsy

Objective:To investigate the effects of chronic VNS on lithium chloride pilocarpine epilepsy model rats,in order to provide a theoretical basis for the prediction and treatment of epileptic seizures in clinical work.Methods:Thirty-six adult male Sprague-Dawley rats were included in the experiment and divided into control group(Ctr group),VNS group(VNS group),epilepsy group(Epi group)and epilepsy+VNS group(Epi+VNS group).Among 36 rats,the levels of 9 cytokines were assessed by MSD(Technology of Meso Scale Discovery)and behavioral data acquisition in 20 rats.The other 16 rats were used for EEG recording and behavioral data acquisition.All data were processed using SPSS 23.0 software package.Results:The changes of epileptic seizure frequency and duration in EPI+VNS group were significantly higher than those in EPI group(P=0.042 and 0.013).In hippocampal tissues,we used one-way ANOVA to find significant differences in the levels of cytokines IL-1β,IL-6,KC/GRO and TNF-α among the four groups(P=0.002,0.005,0.003 and 0.012,respectively).The results showed that the levels of IL-1β,IL-6,KF/GRO and TNF-α in the hippocampus of the EPI group were significantly higher than those of the control group(P=0.005,0.008,0.007 and 0.023,respectively),while the levels of IL-1β,IL-6 and KC/GRO in the EPI+VNS group were significantly lower than those of the EPI group(P=0.015,0.036,0.042,respectively).One-way ANOVA also found significant differences in IL-13 levels among the four groups(P=0.002).The level of IL-13 in the hippocampus of rats in the EPI group was lower than that in the blank control group(P=0.005),while that in the EPI+VNS group was significantly higher than that in the EPI group(P=0.041).In the hypothalamus,there were no significant differences in the levels of cytokines IFN-y,IL-10,IL-13,IL-1β,IL-4,IL-5,IL-6,KC/GRO and TNF-α among the four groups.There was no significant difference in the levels of cytokine Kc/GRO and TNF-α in peripheral blood among the four groups.Conclusion:(1)In terms of behavior,the frequency and duration of epileptic seizures in the epilepsy+VNS group were significantly lower than that in the epilepsy group,suggesting that VNS has anti-epileptic effect on the epileptic rats.(2)The levels of IL-1β,IL-6,TNF-α and KC/GRO cytokines in the hippocampus of rats in epilepsy group were higher than those in the control group,suggesting neuronal damage and inflammatory level in the hippocampus of rats in epilepsy model group.(3)The levels of IL-1β,IL-6 and Kc/GRO in the hippocampus of rats in the epilepsy+VNS group were lower than those in the epilepsy group,suggesting that VNS can improve the inflammatory level in the epileptic foci for 2 weeks,which may be the reason for the improvement of epileptic seizures.(4)The opposite trend of IL-1β,IL-6,Kc/GRO factor and IL-13 factor suggested that VNS may reduce the inflammatory response by promoting M2 polarization of glial cells.