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Combination effects of mesenchymal stem cells transplantation and anodal transcranial direct current stimulation on a cuprizone-induced mouse model of multiple sclerosis

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Abstract

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.

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Acknowledgements

This project was financially supported by Baqiyatallah University of Medical Sciences Grant No. 98000512.

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Authors and Affiliations

  1. Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Sina Mojaverrostami & Alireza Mohammadi

  2. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sina Mojaverrostami, Farnaz Khadivi & Davood Zarini

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  1. Sina Mojaverrostami
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Correspondence to Alireza Mohammadi.

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This article does not contain any studies with human participants performed by any of the authors. All experiments in this study were carried out equally with the guidelines of the Institutional Animal Care and Use Committee (IACUC) and Ethics Committees of Baqiyatallah University of Medical Sciences, Tehran, Iran. Animals were kept in quarantine for approximately 1 week before their use. All animals were kept in standard conditions with unlimited access to food and water. Deep anesthesia was employed for animal surgical procedures.

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Mojaverrostami, S., Khadivi, F., Zarini, D. et al. Combination effects of mesenchymal stem cells transplantation and anodal transcranial direct current stimulation on a cuprizone-induced mouse model of multiple sclerosis. J Mol Histol 53, 817–831 (2022). https://doi.org/10.1007/s10735-022-10092-8

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