ASTROCYTES AFFECT THE SYMPTOMS OF MULTIPLE SCLEROSIS

星形胶质细胞影响多发性硬化症的症状

• 批准号: 3403041
• 负责人: KENNETH J. SMITH
• 金额: $ 15.41万
• 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 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3403041
• 关键词: aminopyridines; astrocytes; axon; calcium channel blockers; cardiac glycosides; diaminopyrimidine; electron microscopy; electrophysiology; histochemistry /cytochemistry; immunochemistry; laboratory rat; multiple sclerosis; myelinopathy; neural conduction; neuropharmacologic agent; neurophysiology; ouabain; remission /regression; sign /symptom; sodium channel; verapamil

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 相互密切而具体地相互作用， 关于无星形胶质细胞脱髓鞘轴突 可能与星形胶质细胞具有不同的生理特性 带鞘的对应物 的生理特性 不含星形胶质细胞的脱髓鞘轴突是未知的。 的假设 有待检验的是是否存在星形胶质细胞 沿着覆盖脱髓鞘的节间可能影响 没有通过病变的传导，以及存在或 异位产生的神经冲动缺失或假性神经冲动 损伤。 这些发现将与多发性硬化症有关 由于MS病变包含许多无星形胶质细胞的脱髓鞘 轴突，特别是在较大病变的中心。 生理学和形态学协议的组合将是 适用于两种类型的中枢性脱髓鞘 损伤。 在一处损伤中，脱髓鞘的轴突保持完全游离 的星胶质细胞接触了许多个月，而在另一个， 轴突被星形胶质细胞单独包裹。 生理 考试将使用急性准备，并长期 植入制剂，以确定导电性能 轴突，包括存在或不存在的传导通过 病变;传导的安全性（如果存在）; 传导长的高频脉冲的纤维; 是否存在异位产生的动作电位： 以及对某些导电性能的影响 作为潜在或有益的药物 MS患者的形态学检查将采用 亲和纯化的抗体（针对分离的大鼠CNS产生 钠通道），以揭示钠通道沿沿着 脱髓鞘的轴突，并比较这种分布与 星形胶质细胞，如果存在的话。 生理特性 所描述的被认为是阴性症状的基础（例如， 麻痹和失明）和阳性症状（如刺痛 感觉异常），MS。这似乎很可能是 星形胶质细胞反应的有效性至少可以决定 部分取决于症状是否缓解。 当然在不无道理的希望，一个更大的 了解神经胶质细胞在病理中的作用 过程和修复可能会导致新的方法，在症状 多发性硬化症和相关疾病的治疗。