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ASTROCYTES AFFECT THE SYMPTOMS OF MULTIPLE SCLEROSIS

星形胶质细胞影响多发性硬化症的症状

基本信息

批准号：
3403042
负责人：
KENNETH J. SMITH
金额：
$ 15.14万
依托单位：
EASTERN VIRGINIA MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1991-11-30
项目状态：
已结题

项目摘要

Since demyelinated central axons and astrocytes are known to interact intimately and specifically with each other, it is pertinent to question whether astrocyte-free demyelinated axons may have different physiological properties from their astrocyte ensheathed counterparts. The physiological properties of astrocyte-free demyelinated axons are not known. The hypothesis to be tested is that the presence or absence of an astroglial covering along a demyelinated internode may affect the presence or absence of conduction through the lesion, and the presence or absence or spurious nervous impulses generated ectopically at the lesion. The findings will be of relevant to multiple sclerosis since the MS lesion contains many astrocytes-free demyelinated axons, especially at the center of the larger lesions. A combination of physiological and morphological protocols will be applied to the examination of two types of central demyelinating lesion. In one lesion, the demyelinated axons remain entirely free of astroglial contacts for many months, whereas in the other, the axons are individually ensheathed by astrocytes. The physiological examination will use both acutely prepared, and chronically implanted preparations to determine the conduction properties of the axons, including the presence or absence of conduction through the lesion; the security of conduction where present; the ability of the fibers to conduct long, high frequency trains of impulses; the presence or absence of ectopically-generated action potentials: and the effects on the conductive properties of certain pharmacological agents advanced as being of potential or a benefit to patients with MS. The morphological examination will employ affinity purified antibodies (raised against isolated rat CNS sodium channel) to reveal the sodium channel distribution along the demyelinated axons, and to compare this distribution with that of the astrocytes, when present. The physiological properties described are believed to underlie the negative symptoms (e.g. paralysis and blindness) and the positive symptoms (e.g. tingling paraesthesia), of MS. It seems quite possible that the effectiveness of the astrocytic response may determine, at least in part, the presence or absence of remissions from the symptoms. Certainly in 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.

由于已知脱髓鞘的中央轴突和星形胶质细胞相互之间的亲密和具体的互动，它是相关问题是不含星形胶质细胞的脱髓鞘轴突可能与它们的星形胶质细胞具有不同的生理特性身穿盔甲的对手。人脑的生理特性不含星形胶质细胞的脱髓鞘轴突尚不清楚。假说需要测试的是星形胶质的存在或不存在沿着脱髓鞘的节间覆盖可能会影响到没有通过病变的传导，并且存在或缺席或虚假的神经冲动产生的异位损伤。这一发现将与多发性硬化症相关由于MS病变包含许多无脱髓鞘的星形胶质细胞轴突，尤指较大病变中心的轴突。生理和形态方案的组合将是应用于两型中枢性脱髓鞘的检查损伤。在一处病变中，脱髓鞘的轴突仍然完全游离。几个月的星形胶质接触，而在另一次，轴突由星形胶质细胞单独包裹。生理学考试将使用敏锐的准备和长期的注入制剂以确定材料的导电性能轴突，包括存在或不存在传导损伤；存在时传导的安全性；能力传导长长的高频脉冲序列的纤维；异位产生的动作电位的存在或不存在：以及对某些材料导电性能的影响。作为潜在的或有益的药物而发展起来的药物对于多发性硬化症患者，形态检查将采用亲和纯化抗体(针对分离的大鼠中枢神经系统提纯钠离子通道)来揭示钠离子通道沿线的分布脱髓鞘轴突，并将这一分布与星形胶质细胞，当存在时。生理特性被认为是阴性症状的基础(例如瘫痪和失明)和阳性症状(如刺痛感觉异常)，这似乎很有可能是星形细胞反应的有效性至少可以决定在某种程度上，症状有无缓解。当然，在不合理的情况下，希望有一个更大的对神经胶质细胞在病理学中作用的认识过程和修复可能会导致新的治疗有症状的方法多发性硬化症及相关疾病的治疗。