Bone marrow mesenchymal stem cells ameliorate intermittent multiple sclerosis: quantitative cerebellar microscopy and functional analysis in cuprizone-induced mice.

Multiple sclerosis (MS) results in histological alterations, which in turn leads to behavioral deficits. Bone marrow mesenchymal stem cells (BMSCs) demonstrate therapeutic potential in MS. This study aimed to assess whether intranasally delivered BMSCs improve cerebellar structure and motor function in an intermittent cuprizone-induced (INT-CPZ) MS model.  METHODS: The mice were divided into five groups: control, CPZ, CPZ + BMSC, INT-CPZ, and INT-CPZ + BMSC. BMSCs were intranasally delivered at weeks 4 and 10. Motor performance was evaluated using beam walking, pole, and ladder rung walking tests. Stereological analyses were performed to estimate cortex and white matter volumes and Purkinje cell number.  RESULTS: BMSC treatment improved motor coordination and balance, particularly in INT-CPZ + BMSC mice, which outperformed the CPZ + BMSC group. Stereological results showed reduced volume loss in cortex and white matter and higher Purkinje cell number in BMSC-treated groups, with INT-CPZ + BMSC showing the most pronounced effect.  CONCLUSION: Intranasal BMSC therapy effectively preserved cerebellar structure and motor function in cuprizone-exposed mice. Intermittent cuprizone exposure enhanced BMSC efficacy, likely through mechanisms involving neuroregeneration, and neuroprotection.