Tissue preconditioning may explain concentric lesions in Balo's type of multiple sclerosis
Tissue preconditioning may explain concentric lesions in Balo's type of multiple sclerosis
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DOI：
10.1093/brain/awh457
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发表时间：
2005-05-01
期刊：
影响因子：
14.5
通讯作者：
Lassmann, H
中科院分区：
文献类型：
--
作者：
Stadelmann, C;Ludwin, S;Lassmann, H
Balo's同心圆硬化症的病变特征是有髓鞘和脱髓鞘组织的交替层。这种多发性硬化症的同心性脱髓鞘的原因尚不清楚。在本研究中，我们调查了14例急性多发性硬化症或慢性多发性硬化症的暴发性加重伴中枢神经系统Balo型病变的患者尸检组织的免疫病理学，重点关注活动性脱髓鞘病变的组织损伤模式。我们发现所有活动性同心圆病变都遵循一种脱髓鞘的模式，这种模式与缺氧样组织损伤相似。这与巨噬细胞和小胶质细胞中诱导型一氧化氮合酶的高表达有关。在边缘的活动性病变，不太一致，在最外层的保存髓鞘，蛋白质参与组织预处理，如缺氧诱导因子1 α和热休克蛋白70，主要表达在少突胶质细胞和星形胶质细胞和巨噬细胞在较小程度上也。由于它们的神经保护作用，这些蛋白质表达的斑块周围组织的边缘可以抵抗扩大病变中的进一步损伤，因此可以保留为保存的有髓鞘组织层。
Lesions of Balo's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Balo-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1 alpha and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.