Blood-Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease
Blood-Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease
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DOI：
10.1002/advs.201900962
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发表时间：
2019-08-12
期刊：
影响因子：
15.1
通讯作者：
Tanzi, Rudolph E.
中科院分区：
文献类型：
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作者：
Shin, Yoojin;Choi, Se Hoon;Tanzi, Rudolph E.
血液中的有害物质通过高度选择性的血脑屏障（BBB）被阻止进入健康的大脑，屏障功能的受损与各种神经系统疾病有关。在阿尔茨海默氏病（AD）中，BBB破坏已被证明甚至在认知能力下降和大脑病理学之前发生。为了研究脑血管系统在AD中的作用，开发了具有BBB样表型的脑内皮细胞单层的生理学相关的3D人神经细胞培养微流体模型。该模型显示概括了在AD患者中观察到的BBB功能障碍的几个关键方面：BBB通透性增加，封闭蛋白-1，封闭蛋白-5和VE-钙粘蛋白的表达降低，基质金属蛋白酶-2和活性氧的表达增加，以及β-淀粉样蛋白（A β）肽在血管内皮的沉积。因此，它为研究BBB功能以及筛选需要通过BBB以进入神经组织的新药提供了一个良好控制的平台。
Harmful materials in the blood are prevented from entering the healthy brain by a highly selective blood-brain barrier (BBB), and impairment of barrier function has been associated with a variety of neurological diseases. In Alzheimer's disease (AD), BBB breakdown has been shown to occur even before cognitive decline and brain pathology. To investigate the role of the cerebral vasculature in AD, a physiologically relevant 3D human neural cell culture microfluidic model is developed having a brain endothelial cell monolayer with a BBB-like phenotype. This model is shown to recapitulate several key aspects of BBB dysfunction observed in AD patients: increased BBB permeability, decreased expression of claudin-1, claudin-5, and VE-cadherin, increased expression of matrix-metalloproteinase-2 and reactive oxygen species, and deposition of beta-amyloid (A beta) peptides at the vascular endothelium. Thus, it provides a well-controlled platform for investigating BBB function as well as for screening of new drugs that need to pass the BBB to gain access to neural tissues.