DO ASTROCYTES AFFECT THE SYMPTOMS OF MULTIPLE SCLEROSIS

星形胶质细胞会影响多发性硬化症的症状吗

• 批准号: 3403040
• 负责人: KENNETH J. SMITH
• 金额: $ 6.22万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1988-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3403040
• 关键词: action potentials; astrocytes; autoradiography; axon; cell free system; electron microscopy; electrophysiology; histology; multiple sclerosis; myelination; myelinopathy; neurophysiology; oligodendroglia; remission /regression; sign /symptom

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.

一类新的中枢性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 中枢神经病变的形态学和生理学检查。 具体来说，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）影响生理 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因素之一影响的纤维特性进行研究 脱髓鞘病变的类别。 每类病变将 以不同类型的神经胶质存在为特征：即 1) 慢性神经胶质细胞脱髓鞘神经纤维（本文介绍 应用见图1）； 2) 神经胶质细胞相关的慢性病变 脱髓鞘神经纤维（中枢白喉毒素病变）； 3）一个 没有神经胶质细胞的稳定病变，神经胶质细胞随后出现 介绍； 4）神经胶质相关纤维的稳定损伤，神经胶质细胞从中 随后去除细胞； 5) 脱髓鞘纤维损伤 进行髓鞘再生（中央溶血卵磷脂损伤）。 这些病变 将进行形态学和电生理学检查。 在形态学上，将检查病变以确定钠 沿着脱髓鞘轴膜的通道分布，并且这种分布 将与周围的神经胶质细胞（如果存在）进行比较。 钠通道将使用本文中引入的新技术进行标记 应用（见图2）。 生理上，不同的病变会 检查： 1) 是否存在通过病灶的传导； 2) 存在时的传导安全； 3) 的能力 纤维异位产生动作电位。 这些生理 属性被认为决定了存在或不存在 阴性症状，如瘫痪和失明，以及产生 阳性症状，如感觉异常。 通过比较得到的结果 通过对不同病变的研究，神经胶质细胞对 应该揭示脱髓鞘的轴突，以及它们对 对脱髓鞘疾病的症状有了更清楚的了解。 在 例如，多发性硬化症的病变，在 星形胶质细胞与不同脱髓鞘轴突的关联程度， 考虑到星形胶质细胞的特性，有必要质疑是否 这种变化可能会导致生理特性的差异 轴突。 例如，星形胶质细胞的有效性可能是 反应可能决定是否存在缓解。 当然， 希望人们更深入地了解其作用并非没有道理 神经胶质细胞的病理过程和修复可能会导致新的 多发性硬化症及相关疾病的对症治疗方法 失调。