Keough Michael B, Jensen Samuel K, Yong V Wee
Department of Clinical Neurosciences, Hotchkiss Brain Institute at University of Calgary.
Department of Clinical Neurosciences, Hotchkiss Brain Institute at University of Calgary; Department of Oncology, Hotchkiss Brain Institute at University of Calgary;
J Vis Exp. 2015 Mar 26(97):52679. doi: 10.3791/52679.
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system characterized by plaque formation containing lost oligodendrocytes, myelin, axons, and neurons. Remyelination is an endogenous repair mechanism whereby new myelin is produced subsequent to proliferation, recruitment, and differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes, and is necessary to protect axons from further damage. Currently, all therapeutics for the treatment of multiple sclerosis target the aberrant immune component of the disease, which reduce inflammatory relapses but do not prevent progression to irreversible neurological decline. It is therefore imperative that remyelination-promoting strategies be developed which may delay disease progression and perhaps reverse neurological symptoms. Several animal models of demyelination exist, including experimental autoimmune encephalomyelitis and curprizone; however, there are limitations in their use for studying remyelination. A more robust approach is the focal injection of toxins into the central nervous system, including the detergent lysolecithin into the spinal cord white matter of rodents. In this protocol, we demonstrate that the surgical procedure involved in injecting lysolecithin into the ventral white matter of mice is fast, cost-effective, and requires no additional materials than those commercially available. This procedure is important not only for studying the normal events involved in the remyelination process, but also as a pre-clinical tool for screening candidate remyelination-promoting therapeutics.
多发性硬化症是一种中枢神经系统的炎性脱髓鞘疾病，其特征是形成含有缺失的少突胶质细胞、髓鞘、轴突和神经元的斑块。髓鞘再生是一种内源性修复机制，即少突胶质细胞前体细胞增殖、募集并分化为形成髓鞘的少突胶质细胞后产生新的髓鞘，这对于保护轴突免受进一步损伤是必要的。目前，所有用于治疗多发性硬化症的疗法都针对该疾病异常的免疫成分，这些疗法可减少炎症复发，但不能阻止疾病进展至不可逆转的神经功能衰退。因此，开发促进髓鞘再生的策略至关重要，这可能会延缓疾病进展，并可能逆转神经症状。存在多种脱髓鞘动物模型，包括实验性自身免疫性脑脊髓炎和 cuprizone；然而，它们在用于研究髓鞘再生方面存在局限性。一种更有效的方法是将毒素局部注射到中枢神经系统，包括将去污剂溶血卵磷脂注射到啮齿动物的脊髓白质中。在本方案中，我们证明将溶血卵磷脂注射到小鼠腹侧白质的手术操作快速、经济高效，并且除了市售材料外无需其他额外材料。该方法不仅对于研究髓鞘再生过程中涉及的正常事件很重要，而且作为筛选促进髓鞘再生的候选治疗药物的临床前工具也很重要。
