Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases
Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases
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DOI：
10.1093/jnen/62.1.25
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Lassmann, H
中科院分区：
文献类型：
--
作者：
Aboul-Enein, F;Rauschka, H;Lassmann, H
髓鞘和少突胶质细胞的破坏导致大的脱髓鞘斑块的形成是多发性硬化症(MS)的病理特征。在一组称为III型的MS患者中，活跃的脱髓鞘病变优先表现为髓鞘相关糖蛋白(MAG)的丢失和凋亡样的少突胶质细胞破坏，而其他髓鞘蛋白保持完好。MAG位于最远端的轴索周围少突胶质细胞突起，在III型病变中，原发的“垂死性”少突胶质细胞病可能是髓鞘变性的起始步骤。在本研究中，研究了各种人类白质病理学，包括急性和慢性白质中风、病毒性脑炎、代谢性脑病和多发性硬化症。除了部分MS病例外，在病毒性脑炎和急性白质卒中的所有病变中也发现了类似的脱髓鞘模式。表现为MAG丢失和凋亡样少突胶质细胞破坏的脑白质病变，无论其原发病原因如何，均可在包括少突胶质细胞在内的各种细胞类型中显著表达低氧诱导因子-let的核表达。我们的数据表明，低氧样组织损伤可能在炎症性脱髓鞘脑损伤的亚组中发挥致病作用。
Destruction of myelin and oligodendrocytes leading to the formation of large demyelinated plaques is the hallmark of multiple sclerosis (MS) pathology. In a subset of MS patients termed pattern III, actively demyelinating lesions show preferential loss of myelin-associated glycoprotein (MAG) and apoptotic-like oligodendrocyte destruction, whereas other myelin proteins remain well preserved. MAG is located in the most distal periaxonal oligodendrocyte processes and primary "dying back" oligodendrogliopathy may be the initial step of myelin degeneration in pattern III lesions. In the present study, various human white matter pathologies, including acute and chronic white matter stroke, virus encephalitis, metabolic encephalopathy, and MS were studied. In addition to a subset of MS cases, a similar pattern of demyelination was found in some cases of virus encephalitis as well as in all lesions of acute white matter stroke. Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-let in various cell types, including oligodendrocytes. Our data suggest that a hypoxia-like tissue injury may play a pathogenetic role in a subset of inflammatory demyelinating brain lesions.