中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1759-1760.doi: 10.4103/1673-5374.169610

• 观点:退行性病与再生 • 上一篇    下一篇

多发性硬化症的神经修复

  

  • 收稿日期:2015-09-15 出版日期:2015-12-07 发布日期:2015-12-07

Perspectives on neuroreparative therapies for treating multiple sclerosis

Junhua Xiao*   

  1. Department of Anatomy and Neuroscience, The University of Melbourne, Victoria, Australia
  • Received:2015-09-15 Online:2015-12-07 Published:2015-12-07
  • Contact: Junhua Xiao, MBBS, Ph.D., xiaoj@unimelb.edu.au.
  • Supported by:

    This work was supported by the Australian National Health and Medical Research Council grants (#APP1058647), National Multiple Sclerosis Society (USA) grant #RG 4309A5/2; Multiple Sclerosis Research Australia Project Fund (#13039), the University of Melbourne Research Grants. The author declares that she has no financial conflicts of interest regarding this manuscript.

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摘要：

多发性硬化症是年轻高加索成人中最常见的神经系统疾病，其主要病理特征包括自身免疫性炎症、脱髓鞘（髓鞘损失）和轴突变性。多发性硬化症损伤的关键细胞类型是少突胶质细胞，其会在中枢神经系统许多轴突周围产生绝缘髓鞘。髓鞘和少突胶质都具有关键作用。髓鞘负责整个许多中枢神经系统的快速推进动作电位，跳跃式传导。
可能是研究结果的相关因素。虽然已经确定了自发髓鞘再生会发生在脱髓鞘损伤后，多发性硬化症中的髓鞘病变程度是可变的；通常多发性硬化症早期髓鞘自发再生相对有效；不过，在稍后阶段许多病变部位都长期处于脱髓鞘状态。这些慢性脱髓鞘病变通常涉及少突胶质祖细胞以及无法分化的少突胶质细胞。这些研究结果表明髓鞘再生不是由缺乏少突胶质细胞祖细胞或它们不能产生少突胶质细胞，而是受限于未能分化为成熟少突胶质细胞，总而形成新髓鞘。今后的工作仍然需要识别能够直接控制髓鞘修复的分子和信号。理解这些分子间的相互作用也许能够破译亲髓鞘和抗髓鞘之间的精确平衡。其中至关重要的是精确确定其基本机制，以确定分子靶标与髓鞘再生的更大选择性，并避免脱靶效应可能影响治疗潜力。新兴的神经修复办法选择性的面向神经系统并增强髓鞘修复能力，也许有一天能够找到急性或急性后期的治疗策略以扭转多发性硬化症攻击造成的伤害。相信在未来，多发性硬化症的治疗方法会将形成联合免疫调节与神经修复的联合策略。目前神经修复疗法仍在研究之中，但极有可能在未来成为多发性硬化症治疗的重要补充手段。

Abstract:

Multiple sclerosis (MS) is the most common neurological disease of young Caucasian adults. This disease is characterized by inflammatory demyelination of the central nervous system (CNS) and involves activation of key inflammatory cells of both the adaptive and innate immune systems, which target and destroy both myelin and oligodendrocytes (the myelin-forming glial cells in the CNS). Key pathological features of the disease include autoimmune inflammation, demyelination (myelin loss) and axonal degeneration. The key cell type damaged in MS is oligodendrocytes, which produce the insulating myelin sheath surrounding many axons in the CNS. Myelin and oligodendrocytes have critical roles. Myelin is responsible for promoting rapid, saltatory conduction of action potentials throughout much of the CNS. When myelin is lost in diseases such as MS, saltatory conduction is disrupted and conduction block can ensue. Myelin also provides a physical barrier for axons and thus serves to abrogate axonally directed, immune attack. Oligodendrocytes can also provide key nutritive support to axons in the healthy, quiescent state, which is compromised when oligodendrocytes are targeted. There is an emerging consensus that the progressive disability that ultimately ensues for many patients with MS correlates with the degree of accumulative axonal degeneration. It is also apparent that the extent of demyelination, and the degree of oligodendrocyte targeting, are likely to be relevant factors that dictate outcomes. Whilst it is well identified that spontaneous remyelination occurs after a demyelinative insult, the degree of remyelination within MS lesions is variable; generally MS lesions remyelinate relatively efficiently early on in disease; however, at later stages many lesions remain chronically demyelinated. These chronically demyelinated lesions typically contain oligodendrocyte progenitor cells (OPCs) and premyelinating oligodendrocytes that have “stalled” in their differentiation. These findings suggest remyelination is not limited by an absence of oligodendrocyte progenitors or their failure to generate oligodendrocytes, but a failure to differentiate into mature oligodendrocytes and to initiate new myelin formation.