Yamazaki Reiji, Ohno Nobuhiko
Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
Division of Ultrastructural Research, National Institute for Physiological Sciences, Okazaki, Japan.
Acta Histochem Cytochem. 2024 Feb 29;57(1):1-5. doi: 10.1267/ahc.24-00005. Epub 2024 Feb 23.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterized by remyelination failure and axonal dysfunction. Remyelination by oligodendrocytes is critical for improvement of neurological deficits associated with demyelination. Rodent models of demyelination are frequently used to develop and evaluate therapies for MS. However, a suitable mouse model for assessing remyelination-associated recovery of motor functions is currently unavailable. In this review, we describe the development of the mouse model of internal capsule (IC) demyelination by focal injection of lysolecithin into brain and its application in the evaluation of drugs for demyelinating diseases. This mouse model exhibits motor deficits and subsequent functional recovery accompanying IC remyelination. Notably, this model shows enhancement of functional recovery as well as tissue regeneration when treated with clemastine, a drug that promotes remyelination. The IC demyelination mouse model should contribute to the development of novel drugs that promote remyelination and ameliorate neurological deficits in demyelinating diseases.
多发性硬化症（MS）是一种中枢神经系统的炎性脱髓鞘疾病，其特征为髓鞘再生失败和轴突功能障碍。少突胶质细胞进行的髓鞘再生对于改善与脱髓鞘相关的神经功能缺损至关重要。脱髓鞘的啮齿动物模型常被用于开发和评估MS的治疗方法。然而，目前尚无用于评估与髓鞘再生相关的运动功能恢复的合适小鼠模型。在本综述中，我们描述了通过向脑内局灶注射溶血卵磷脂建立内囊（IC）脱髓鞘小鼠模型的过程及其在脱髓鞘疾病药物评估中的应用。该小鼠模型表现出运动功能缺损以及伴随IC髓鞘再生的后续功能恢复。值得注意的是，当用促进髓鞘再生的药物氯马斯汀治疗时，该模型显示出功能恢复以及组织再生的增强。IC脱髓鞘小鼠模型应有助于开发促进髓鞘再生并改善脱髓鞘疾病神经功能缺损的新型药物。
