Barac-Latas V, Suchanek G, Breitschopf H, Stuehler A, Wege H, Lassmann H
Department of Physiology and Immunology, University of Rijeka, Croatia.
Glia. 1997 Jan;19(1):1-12. doi: 10.1002/(sici)1098-1136(199701)19:1<1::aid-glia1>3.0.co;2-5.
Intracerebral infection of rats with JHM coronavirus induces a chronic inflammatory demyelinating disease, which in many respects mimicks the pathology of multiple sclerosis. We investigated the patterns of demyelination and oligodendrocyte pathology in this model. In early stages of the disease infection of oligodendrocytes was associated with a downregulation of expression of mRNA for proteolipid protein in the absence of myelin destruction. When demyelinating lesions were formed infected oligodendrocytes were destroyed by necrosis, whereas oligodendrocytes that did not contain detectable virus antigen or RNA were in part dying by apoptosis. At this stage of the disease remyelination of the lesions was pronounced. At later stages after infection virus antigen was nearly completely cleared from the lesions. In spite of the lack of detectable virus, ongoing demyelination and unspecific tissue destruction occurred, and oligodendrocytes were mainly destroyed by apoptosis. These late lesions revealed only minimal central remyelination, but they were frequently repaired by Schwann cells. Our studies suggest that the mechanisms of myelin destruction in this model of virus-induced demyelination are complex and that the patterns of tissue damage may change during the course of the disease.
用JHM冠状病毒对大鼠进行脑内感染会诱发一种慢性炎性脱髓鞘疾病，该疾病在许多方面模拟了多发性硬化症的病理特征。我们研究了此模型中脱髓鞘和少突胶质细胞病理变化的模式。在疾病早期，少突胶质细胞感染与髓磷脂未被破坏情况下蛋白脂蛋白mRNA表达下调有关。当形成脱髓鞘病变时，被感染的少突胶质细胞因坏死而被破坏，而未检测到病毒抗原或RNA的少突胶质细胞部分则通过凋亡死亡。在疾病的这个阶段，病变的再髓鞘化很明显。感染后的后期，病毒抗原几乎完全从病变中清除。尽管未检测到病毒，但仍持续发生脱髓鞘和非特异性组织破坏，少突胶质细胞主要通过凋亡被破坏。这些晚期病变仅显示出极少的中央再髓鞘化，但它们经常由施万细胞修复。我们的研究表明，在这种病毒诱导的脱髓鞘模型中，髓磷脂破坏机制很复杂，并且组织损伤模式可能在疾病过程中发生变化。
