Combination Effects of Mesenchymal Stem Cells Transplantation and Anodal Transcranial Direct Current Stimulation on a Cuprizone-induced Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) has no absolute treatment, and researchers are still exploring to introduce promising therapy for MS. Transcranial direct current stimulation (tDCS), is a safe, non-invasive procedure for brain stimulating which can enhance working memory, cognitive neurohabitation and motor recovery. Here, we evaluated the effects of tDCS treatment and Mesenchymal stem cells (MSCs) transplantation on remyelination ability of a Cuprizone (CPZ)-induced demyelination mouse model. tDCS significantly increased the motor coordination and balance abilities in CPZ + tDCS and CPZ + tDCS + MSCs mice in comparison to the CPZ mice. Luxol fast blue (LFB) staining showed that tDCS and MSCs transplantation could increase remyelination capacity in CPZ + tDCS and CPZ + MSCs mice compared to the CPZ mice. But, the effect of tDCS with MSCs transplantation on remyelination process was larger than each of treatment alone. Immunofluorescence technique indicated that the numbers of Olig2 cells were increased by tDCS and MSCs transplantation in CPZ + tDCS and CPZ + MSCs mice compared to the CPZ mice. Interestingly, the combination effect of tDCS and MSCs was larger than each of treatment alone on Oligodendrocytes population. MSCs transplantation significantly decreased the TUNEL cells in CPZ + MSCs and CPZ + tDCS + MSCs mice in comparison to the CPZ mice. Also, the combination effects of tDCS and MSCs transplantation was much larger than each of treatment alone on increasing the mRNA expression of BDNF and Sox2, while decreasing P53 as compared to CPZ mice. It can be concluded that the combination usage of tDCS and MSCs transplantation enhance remyelination process in CPZ-treated mice by increasing transplanted stem cell homing, oligodendrocyte generation and decreasing apoptosis.