DO ASTROCYTES AFFECT THE SYMPTOMS OF MULTIPLE SCLEROSIS

一类新的中枢脱髓鞘病变和一种新的标记方法 钠通道沿神经的分布，将应用于 中枢神经病的形态和生理检查。 具体地说，该项目将研究神经胶质细胞的潜在作用。 细胞(星形胶质细胞和少突胶质细胞)对生理学的影响 病理性中枢神经纤维的特性。这个角色将是 通过比较受以下五种影响之一的纤维的性能来进行研究 脱髓鞘病变的分类。每一类损伤都将是 以不同类型的胶质细胞存在为特征的：即1)病变 慢性无神经胶质细胞脱髓鞘神经纤维(介绍于 应用见图1)；2)慢性神经胶质细胞相关病变 脱髓鞘神经纤维(中央白喉毒素损伤)；3)a 无神经胶质细胞的稳定病变，神经胶质细胞较晚到达 介绍；4)胶质相关纤维的稳定病变 细胞随后被移除；以及5)脱髓鞘纤维病变 进行再髓鞘形成(中央溶血磷脂病变)。这些损伤 将从形态和电生理两方面进行检查。 在形态上，将检查皮损以确定钠 沿脱髓鞘轴膜的经络分布及这种分布 将与周围的神经胶质细胞(如果存在)进行比较。 将使用一种新的技术来标记钠离子通道 应用程序(参见图2)。从生理上讲，不同的损伤 检查：1)有无通过病变的传导； 2)传导存在时的安全性；以及3)连接的能力 纤维以异位方式产生动作电位。这些生理上的 属性被认为决定了是否存在 瘫痪和失明等阴性症状，以及 阳性症状，如感觉异常。通过比较所获得的结果 通过对不同病变的研究，神经胶质细胞在脑内的潜在作用 脱髓鞘轴突应该被揭示，以及它们对 对脱髓鞘病的症状学有了更清晰的认识。在 以多发性硬化症的病变为例， 星形胶质细胞与不同脱髓鞘轴突的联系程度， 考虑到星形胶质细胞的特性，我们有必要质疑 这种变异可能会导致不同的生理特性 轴突。例如，星形胶质细胞的有效性可能 反应可决定是否有缓解。当然, 希望能更好地理解 神经胶质细胞在病理过程和修复中可能导致新的 多发性硬化症的对症治疗及相关研究进展 精神错乱。

A new class of central demyelinating lesion, and a new method of marking the sodium channel distribution along nerves, will be applied to a morphological and physiological examination of central neuropathy. Specifically, the project will examine the potential role of neuro-glial cells (astrocytes and oligodendrocytes) in influencing the physiological properties of pathological central nerve fibres. This role will be investigated by comparing the properties of fibers affected by one of five classes of demyelinating lesion. Each class of lesion will be characterised by a different type of glial presence: namely 1) a lesion of chroncially glial cell-free demyelinated nerve fibers (introduced in this application see figure 1); 2) a lesion of chronically glial cell-associated demyelinated nerve fibers (the central diphtheria toxin lesion); 3) a stable lesion free of glial cells to which glial cells are later introduced; 4) a stable lesion of glial-associated fibers from which glial cells are later removed; and 5) a lesion in which the demyelinated fibers undergo remyelination (the central lysolecithin lesion). These lesions will be examined both morphologically and electrophysiologically. Morphologically, the lesions will be examined to determine the sodium channel distribution along the demyelinated axolemma, and this distribution will be compared with that of the surrounding glial cells (when present). The sodium channels will be marked using a new technique introduced in this application (see figure 2). Physiologically, the different lesions will be examined for: 1) the presence or absence of conduction through the lesion; 2) the security of the conduction when present; and 3) the ability of the fibers to generate action potentials ectopically. These physiological properties are believed to determine both the presence or absence of negative symptoms such as paralysis and blindness, and the generation of positive symptoms such as paraesthesiae. By comparing the results obtained from study of the different lesions the potential effects of glial cells on demyelinated axons should be revealed, and their contribution to the symptomatology of demyelinating disease more clearly understood. In the lesion of multiple sclerosis for example, there is a marked variation in the degree of association of astrocytes to different demyelinated axons, and considering the properties of astrocytes it is pertinent to question if this variation may cause differences in the physiological properties of the axons. It is for example possible that the effectiveness of the astrocyte response may determine the presence or absence of remissions. Certainly, it is not unreasonable to hope that a greater understanding of the role of neuro-glial cells in pathological processes and repair may lead to new approaches in the symptomatic therapy of multiple sclerosis and related disorders.