血脑屏障
紧密连接
神经科学
势垒函数
阿尔茨海默病
医学
基质金属蛋白酶
病理
细胞生物学
疾病
生物
中枢神经系统
内科学
作者
Yoojin Shin,Se Hoon Choi,Eun‐Hee Kim,Enjana Bylykbashi,Jeong Ah Kim,Seok Chung,Doo Yeon Kim,Roger D. Kamm,Rudolph E. Tanzi
标识
DOI:10.1002/advs.201900962
摘要
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 β-amyloid (Aβ) 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.
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