Mammalian Target of Rapamycin (mTOR) Inhibitor Improves Local Immune Microenvironment and Reduces Seizures via Increasing miR-211 Level in Rat Brain

Abstract

This study aims to analyze the role of mTOR inhibitor on the expression of miR-211 in rat brain tissue and the biological effect of miR-211 in attenuating seizure. Rats were randomly divided into four groups, and the number of seizures and the duration of single seizure were observed within 24 hours after intervention. The level of miR-211 in brain tissue was detected by RT qPCR, the apoptosis of nerve cells was assessed by TUNEL staining, the level of immune cells was detected by flow cytometry, and the level of serum inflammatory factors was determined by ELISA. The number of seizures and the duration of single seizure in the three groups treated by rapamycin within 24 hours were lower than those in the control group, and the symptom relief in group C was the best. After treatment, the expression level of miR-211 in the brain tissue of epileptic rats increased. TUNEL staining showed that neuronal apoptosis was obvious in epileptic rats. The anti apoptotic ability of group C was the most significant, followed by group D and group B. Compared with group A, the levels of CD3+ cells, CD8+ cells and CD4+/CD25+ cells in brain tissue of group C were decreased, while the levels of IL-2 and IFN-γ were lower in group C than those in control. In group C (n = 5), the levels of CD3+ cells, CD8+ cells and CD4+/CD25+ cells were elevated, and the levels of immune related cytokines IL-2 and IFN-γ were higher than those of rats without miR-211 inhibition. mTOR inhibitors can improve the local immune microenvironment, reduce the release of inflammatory factors, and finally decrease the frequency and duration of seizures by up regulating the level of miR-211 in rat brain tissue.