Effect of Bone Marrow Stromal Stem Cells (BMSCs) Therapy on the Expression of Sodium Channel, Voltage-Gated, Type I, Alpha Subunit (SCN1A) in Temporal Lobe Epilepsy and Its Mechanism

Abstract

SCN1A gene plays an indispensable role in several diseases. Bone marrow stromal stem cells (BMSCs) therapy is a potential target for treating epilepsy, but its therapeutic effect and mechanism is unclear. Our study aims to investigate the mechanism by how BMSCs affect epilepsy. Wistar rats were assigned into control group, model group (pilocarpine-induced TLE model), and BMSCs group followed by measuring the latency of field excitatory postsynaptic potential, pathological changes, SCN1A level by Real time PCR, NF-ĸB and TLR4 expression by Western blot, and HGMB1, TLR4, IL-1β and IL-6 secretion by ELISA. In model group, the incubation period of postsynaptic potential generation was significantly shortened and SCN1A level was significantly decreased, along with increased NF-ĸB expression and secretion of HMGB1, TLR-4, IL-1β and IL-6 (P < 0.05). After BMSCs treatment, the incubation period of postsynaptic potentials can be significantly prolonged and SCN1A was significantly upregulated, with ameliorated epilepsy injury and reduced secretion of related factors (P <0.05). Pilocarpine-induced TLE can reduce SCN1A expression and BMSCs therapy can up-regulate SCN1A expression by regulating NF-ĸB/HGMB1/TLR4 signaling pathway, thereby protecting neurons, reducing pathological damage, and ameliorating the development of epilepsy.