The blood–brain barrier is a dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma. Specialized brain endothelial cells, astrocytes, neurons, microglia and pericytes together compose the neurovascular unit and interact to maintain blood–brain barrier function. A disturbed brain barrier function is reported in most common neurological disorders and may play a role in disease pathogenesis. However, a comprehensive overview of how the neurovascular unit is affected in a wide range of rare disorders is lacking. Our aim was to provide further insights into the neuropathology of the neurovascular unit in leukodystrophies to unravel its potential pathogenic role in these diseases. Leukodystrophies are monogenic disorders of the white matter due to defects in any of its structural components. Single leukodystrophies are exceedingly rare, and availability of human tissue is unique. Expression of selective neurovascular unit markers such as claudin-5, zona occludens 1, laminin, PDGFRβ, aquaporin-4 and α-dystroglycan was investigated in eight different leukodystrophies using immunohistochemistry. We observed tight junction rearrangements, indicative of endothelial dysfunction, in five out of eight assessed leukodystrophies of different origin and an altered aquaporin-4 distribution in all. Aquaporin-4 redistribution indicates a general astrocytic dysfunction in leukodystrophies, even in those not directly related to astrocytic pathology or without prominent reactive astrogliosis. These findings provide further evidence for dysfunction in the orchestration of the neurovascular unit in leukodystrophies and contribute to a better understanding of the underlying disease mechanism.

中文翻译：

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脑白质营养不良中神经血管单元的病理学

血脑屏障是大脑微血管系统中的动态内皮细胞屏障，它将血液与脑实质分开。专门的脑内皮细胞、星形胶质细胞、神经元、小胶质细胞和周细胞共同构成神经血管单元，并相互作用以维持血脑屏障功能。在最常见的神经系统疾病中报告了脑屏障功能紊乱，并可能在疾病发病机制中发挥作用。然而，缺乏对神经血管单元如何在广泛的罕见疾病中受到影响的全面概述。我们的目的是进一步深入了解脑白质营养不良中神经血管单元的神经病理学，以阐明其在这些疾病中的潜在致病作用。脑白质营养不良是由于白质任何结构成分的缺陷而导致的单基因疾病。单一的脑白质营养不良极为罕见，人体组织的可用性是独一无二的。使用免疫组织化学在八种不同的脑白质营养不良中研究了选择性神经血管单位标记物的表达，例如 claudin-5、zona occludens 1、层粘连蛋白、PDGFRβ、aquaporin-4 和 α-dystroglycan。我们观察到紧密连接重排，表明内皮功能障碍，八分之五的评估不同来源的脑白质营养不良和改变的水通道蛋白 4 分布。Aquaporin-4 重新分布表明脑白质营养不良中的一般星形胶质细胞功能障碍，即使在那些与星形胶质细胞病理学没有直接关系或没有显着反应性星形胶质细胞增生症的患者中也是如此。