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: 3403039
• 负责人: KENNETH J. SMITH
• 金额: $ 5.9万
• 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 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3403039
• 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.

一种新的中枢性脱髓鞘病变分类及标记方法