Abstract:
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.
摘要:
多发性硬化症(MS)是中枢神经系统的炎症性脱髓鞘疾病,以髓鞘再生失败和轴突功能障碍为特征。少突胶质细胞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经常用于开发和评估MS的治疗方法。然而,目前尚无合适的用于评估髓鞘再生相关运动功能恢复的小鼠模型.在这次审查中,我们描述了通过向脑内局部注射溶血卵磷脂来开发内囊(IC)脱髓鞘小鼠模型及其在评估脱髓鞘疾病药物中的应用。该小鼠模型表现出伴随IC髓鞘再生的运动缺陷和随后的功能恢复。值得注意的是,该模型显示,当用氯马斯汀治疗时,功能恢复和组织再生的增强,一种促进髓鞘再生的药物.IC脱髓鞘小鼠模型应有助于开发促进髓鞘再生和改善脱髓鞘疾病中的神经功能缺损的新型药物。