Related Experiment Video
Updated: Aug 11, 2025
Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in
Reiji Yamazaki1, Yasuyuki Osanai2, Tom Kouki2
1Department of Biology and Center for Cell Reprogramming, Georgetown University, Washington, DC, 20057, USA; Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
Abstract:
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.
Insights
Clemastine improved motor function and promoted remyelination in a mouse model of central nervous system demyelination. This study validates the internal capsule demyelination model for testing therapies for multiple sclerosis (MS).
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a central nervous system inflammatory demyelinating disease with failed remyelination and axonal degeneration.
- Animal models are crucial for evaluating MS therapies, but their utility in assessing remyelination-promoting drugs needs validation.
- A previously established mouse model of focal internal capsule (IC) demyelination showed motor deficits and recovery.
Purpose of the Study:
- To investigate the efficacy of clemastine, a remyelination-promoting drug, in the lysophosphatidylcholine-induced IC demyelination mouse model.
- To assess the utility of this model for evaluating pharmacological treatments that enhance remyelination and motor function recovery.
Main Methods:
- Induction of focal demyelination in the mouse internal capsule using lysophosphatidylcholine injection.
- Administration of clemastine or vehicle (PBS) to demyelinated mice.
- Evaluation of motor function using behavioral tests and histological analysis of IC lesions.
Main Results:
- Clemastine treatment significantly improved motor function and altered forepaw preference in demyelinated mice.
- Histological analysis revealed increased mature oligodendrocyte density, reduced axonal injury, and enhanced myelination in clemastine-treated mice.
- Increased myelinated axon number and myelin thickness were observed in the IC lesions of clemastine-treated group compared to controls.
Conclusions:
- The lysophosphatidylcholine-induced IC demyelination model is effective for evaluating motor function changes induced by remyelination-promoting therapies.
- Clemastine demonstrates therapeutic potential by improving motor deficits and promoting remyelination in this MS model.
- This model provides a valuable platform for preclinical testing of novel MS treatments targeting remyelination.
