Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in mice

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system characterized by remyelination failure, axonal degeneration, and progressive worsening of motor functions. Animal models of demyelination are frequently used to develop and evaluate therapies for MS. We recently reported that focal internal capsule (IC) demyelination in mice with lysophosphatidylcholine injection induced acute motor deficits followed by recovery through remyelination. However, it remains unknown whether the IC demyelination mouse model can be used to evaluate changes in motor functions caused by pharmacological treatments that promote remyelination using behavioral testing and histological analysis. In this study, we examined the effect of clemastine, an anti-muscarinic drug that promotes remyelination, in the mouse IC demyelination model. Clemastine administration improved motor function and changed forepaw preference in the IC demyelinated mice. Moreover, clemastine-treated mice showed increased mature oligodendrocyte density, reduced axonal injury, an increased number of myelinated axons and thicker myelin in the IC lesions compared with control (PBS-treated) mice. These results suggest that the lysophosphatidylcholine-induced IC demyelination model is useful for evaluating changes in motor functions following pharmacological treatments that promote remyelination.

 

Comments：

It is encouraging to learn that clemastine, an anti-muscarinic drug that has been shown to promote remyelination, improved motor function and changed forepaw preference in the IC demyelinated mice. The observation that clemastine-treated mice had increased mature oligodendrocyte density, reduced axonal injury, an increased number of myelinated axons, and thicker myelin in the IC lesions compared to control mice is also promising.

The study suggests that the lysophosphatidylcholine-induced IC demyelination model is a useful tool for evaluating the effects of pharmacological treatments that promote remyelination on motor function and histological changes. This could have implications for the development and evaluation of potential therapies for multiple sclerosis and other demyelinating disorders.

Overall, the findings of this study are significant and contribute to our understanding of the mechanisms underlying demyelination and remyelination and the potential of pharmacological interventions to promote remyelination and improve motor function.

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