Ferguson B, Matyszak M K, Esiri M M, Perry V H
Department of Pharmacology, Oxford University, UK.
Brain. 1997 Mar;120 ( Pt 3):393-9. doi: 10.1093/brain/120.3.393.
One of the histological hallmarks of early multiple sclerosis lesions is primary demyelination, with myelin destruction and relative sparing of axons. On the other hand, it is widely accepted that axonal loss occurs in, and is responsible for, the permanent disability characterizing the later chronic progressive stage of the disease. In this study, we have used an antibody against amyloid precursor protein, known to be a sensitive marker of axonal damage in a number of other contexts, in immunocytochemical experiments on paraffin embedded multiple sclerosis lesions of varying ages in order to see at which stage of the disease axonal damage, in addition to demyelination, occurs and may thus contribute to the development of disability in patients. The results show the expression of amyloid precursor protein in damaged axons within acute multiple sclerosis lesions, and in the active borders of less acute lesions. This observation may have implications for the design and timing of therapeutic intervention, one of the most important aims of which must be the reduction of permanent disability.
早期多发性硬化症病变的组织学特征之一是原发性脱髓鞘,即髓鞘破坏而轴突相对保留。另一方面,人们普遍认为轴突丢失发生在疾病的慢性进展后期,并导致了该阶段的永久性残疾。在本研究中,我们使用了一种针对淀粉样前体蛋白的抗体,已知该抗体在许多其他情况下是轴突损伤的敏感标志物,对不同年龄的石蜡包埋多发性硬化症病变进行免疫细胞化学实验,以观察除脱髓鞘外,轴突损伤在疾病的哪个阶段发生,从而可能导致患者残疾的发展。结果显示,淀粉样前体蛋白在急性多发性硬化症病变内受损轴突以及不太急性病变的活跃边缘表达。这一观察结果可能对治疗干预的设计和时机有影响,其中最重要的目标之一必须是减少永久性残疾。