The Role And Mechanism Of MicroRNA-155 In The Pathogenesis Of Epilepsy

Objective:MicroRNA-155(miR-155)plays an important role in immune and inflammatory processes,but it is unclear whether miR-155-mediated inflammation is involved in the development of epilepsy.In this paper,the role of miR-155 in the process of epilepsy was studied by kainic acid(KA)-induced epilepsy in animal and cell models,Furthermore,the results of the animal model were verified in the blood of epileptic patients,hoping to explore new biomarkers to solve clinical problems.Methods:The epileptic model was induced by intraperitoneal injection of c57b1/6 mice and Ka-treated primary cells,using a large number of experiments like electroencephalogram monitoring,lateral ventricle stereotaxy,extraction of protein and RNA,real-time fluorescence quantitative PCR,Western blot,primary cell culture,and FJB staining to study the expression level,distribution,target genes and so on of miR-155.And in the blood of patients with epilepsy,miRNAs were extracted to verify the expression of miR-155 by real-time PCR.Results:In a successful mouse model of epilepsy,the expression of miR-155 in the hippocampus of epileptic mice was significantly higher than that in the control group(Ctrl group).The electroencephalogram showed that epileptic waves appeared in mice in the experimental group(KA group)changed significantly.After intraventricular injection of the miR-155 antagomir,we found that the frequency and amplitude of epileptic waves in KA+ antagomir group electroencephalograms were lower than those in KA group,in the FJB staining,there were more necrotic neurons in the CA2 region of the KA group than in the control group,and the KA+ antagomir group was decreased;In a successful epilepsy cell model,miR-155 is more highly expressed in microglial cells than in neurons.the expression of miR-155 is significantly up-regulated in time gradients treated with 50?M KA,and Through experimental validation of multiple predicted target genes,it was found that Csflr was significantly down-regulated with time,and the expression level of Csflr in KA+antagomir group was higher than that in Ctrl group;in the blood of patients with epilepsy,miR-155 expression levels were significantly elevated compared with healthy controls.Conclusions:MiR-155 is involved in inflammation-promoting epilepsy by inducing microglial cells and the target gene is Csflr;application of miR-155 antagomir can reduce seizures,improve electroencephalogram discharge,and reduce neuronal damage;the level of miR-155 in the blood may be a potential biomarker for epilepsy,and silencing miR-155 in microglia may be a therapeutic strategy for epilepsy.