Ozawa K, Suchanek G, Breitschopf H, Brück W, Budka H, Jellinger K, Lassmann H
Research Unit for Experimental Neuropathology, Austrian Academy of Sciences, Wien.
Brain. 1994 Dec;117 ( Pt 6):1311-22. doi: 10.1093/brain/117.6.1311.
Patterns of inflammation, demyelination and oligodendrocyte pathology were studied in acute multiple sclerosis and during early and late exacerbations of chronic multiple sclerosis. Cells within lesions were identified by immunocytochemistry with markers for T lymphocytes, macrophages, oligodendrocytes and astrocytes. In addition, in situ hybridization for proteolipid protein mRNA was used to identify myelinating and myelin supporting oligodendrocytes. Degenerating cells in the lesions were detected by DNA fragmentation in cell nuclei. The inflammatory reaction in all three types of multiple sclerosis lesions was shown to be dominated by T lymphocytes and macrophages. In late chronic multiple sclerosis lesions, a significant increase in the number of immunoglobulin producing plasma cells was found in infiltrates as compared with acute and early multiple sclerosis lesions. In all three types of multiple sclerosis, confluent plaques of demyelination were found to be present. In acute multiple sclerosis, demyelination was found to be associated with extensive destruction of other tissue elements, including oligodendrocytes, astrocytes and axons, but even in these destructive lesions a considerable number of oligodendrocytes was preserved and at disposal therefore, for rapid remyelination. During early exacerbations of chronic multiple sclerosis, selective demyelination was associated with almost complete preservation of oligodendrocytes in the majority of cases. Correspondingly, a high number of remyelinating lesions was present at that stage of disease. In lesions developing late after onset of multiple sclerosis, demyelination generally accompanied extensive destruction and loss of oligodendrocytes. In these lesions, remyelination was sparse and restricted to lesional borders. The observed patterns of cell death suggest that in some cases oligodendrocytes, in others myelin sheaths are the primary target of the destructive process. Our data indicate that the type and amount of inflammation, de- and remyelination, and of tissue damage vary between different forms of multiple sclerosis and between different stages of the disease, possibly reflecting different pathogenic mechanisms in a disease spectrum.
研究了急性多发性硬化症以及慢性多发性硬化症早期和晚期病情加重时的炎症、脱髓鞘和少突胶质细胞病变模式。通过免疫细胞化学方法，使用针对T淋巴细胞、巨噬细胞、少突胶质细胞和星形胶质细胞的标志物来识别病变内的细胞。此外，利用蛋白脂蛋白mRNA的原位杂交技术来识别正在形成髓鞘和支持髓鞘的少突胶质细胞。通过细胞核中的DNA片段化检测病变中的退化细胞。结果显示，所有三种类型的多发性硬化症病变中的炎症反应均以T淋巴细胞和巨噬细胞为主。与急性和早期多发性硬化症病变相比，在晚期慢性多发性硬化症病变的浸润物中发现产生免疫球蛋白的浆细胞数量显著增加。在所有三种类型的多发性硬化症中，均发现有融合的脱髓鞘斑块。在急性多发性硬化症中，脱髓鞘与包括少突胶质细胞、星形胶质细胞和轴突在内的其他组织成分的广泛破坏有关，但即使在这些破坏性病变中，仍保留了相当数量的少突胶质细胞，因此可用于快速再髓鞘化。在慢性多发性硬化症的早期病情加重期间，在大多数情况下，选择性脱髓鞘与少突胶质细胞几乎完全保留有关。相应地，在疾病的该阶段存在大量再髓鞘化病变。在多发性硬化症发病后期形成的病变中，脱髓鞘通常伴随着少突胶质细胞的广泛破坏和丧失。在这些病变中，再髓鞘化稀疏且局限于病变边界。观察到的细胞死亡模式表明，在某些情况下少突胶质细胞是破坏过程的主要靶点，而在另一些情况下髓鞘则是主要靶点。我们的数据表明，不同形式的多发性硬化症以及疾病的不同阶段，炎症、脱髓鞘和再髓鞘化以及组织损伤的类型和程度各不相同，这可能反映了疾病谱中不同的致病机制。
