Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE
Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE
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DOI：
10.1016/j.jneuroim.2010.08.011
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发表时间：
2010-12-15
影响因子：
3.3
通讯作者：
McQuaid, Stephen
中科院分区：
文献类型：
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作者：
Bennett, Jami;Basivireddy, Jayasree;McQuaid, Stephen
多发性硬化症 (MS) 是一种脱髓鞘疾病，其特征是血脑屏障 (BBB) 破坏和中枢神经系统炎症浸润积聚。紧密连接是特殊的细胞间粘附结构，也是血脑屏障的关键组成部分，此前已被证明在多发性硬化症组织中分布异常。为了评估实验性自身免疫性脑脊髓炎 (EAE) 是否为 MS 疾病的这一方面提供了合适的模型，我们检查了 ZO-1 在 EAE 病程中的表达和分布。我们观察到 ZO-1 发生显着的重新定位，这种重新定位发生在明显的临床疾病之前，并且与炎症细胞积聚的部位相关。用EAE诱导成分处理小鼠脑内皮细胞的体外培养物提供了类似的发现，ZO-1重新定位并且内皮单层的通透性增加。 EAE 模型中的 BBB 破坏似乎与 MS 的疾病进展平行，对脑血管内皮有直接影响，使其成为未来评估 MS 样病理学中紧密连接破坏和修复的理想工具。 (C) 2010 Elsevier B.V. 保留所有权利。
Multiple sclerosis (MS) is a demyelinating disease characterized by the breakdown of the blood-brain barrier (BBB), and accumulation of inflammatory infiltrates in the central nervous system. Tight junctions are specialized cell-cell adhesion structures and critical components of the BBB that have previously been shown to be abnormally distributed in MS tissue. To evaluate whether experimental autoimmune encephalomyelitis (EAE) provides a suitable model for this aspect of MS disease, we examined the expression and distribution of ZO-1 over the course of disease in EAE. We observed a dramatic relocalization of ZO-1 which precedes overt clinical disease and correlates with the sites of inflammatory cell accumulation. Treatment of in vitro cultures of murine brain endothelial cells with components of EAE induction provided similar findings, with relocalization of ZO-1 and increased permeability of endothelial monolayers. BBB disruption in the EAE model appears to parallel disease progression in MS, with direct effects on the cerebrovascular endothelium, making it an ideal tool for future evaluation of tight junction breakdown and repair in MS-like pathology. (C) 2010 Elsevier B.V. All rights reserved.