Blood-Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease

被引：225

作者：

Shin, Yoojin ^{[1
]}

Choi, Se Hoon ^{[2
]}

Kim, Eunhee ^{[2
]}

Bylykbash, Enjana ^{[2
]}

Kim, Jeong Ah ^{[3
,4
]}

Chung, Seok ^{[5
,6
]}

Kim, Doo Yeon ^{[2
]}

Kamm, Roger D. ^{[1
,7
,8
]}

Tanzi, Rudolph E. ^{[2
]}

机构：

[1] MIT, Dept Mech Engn, 500 Technol Sq,MIT Bldg,Room NE47-321, Cambridge, MA 02139 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit,McCance Ctr Brain Hlth,Mas, Charlestown, MA 02129 USA

[3] Korea Basic Sci Inst, Biomed Omics Grp, Cheongju 28119, South Korea

[4] Univ Sci & Technol, Dept Bioanalyt Sci, Daejeon 34113, South Korea

[5] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul 02841, South Korea

[6] Korea Univ, Sch Mech Engn, Seoul 02841, South Korea

[7] MIT, Dept Biol Engn, 500 Technol Sq,MIT Bldg,Room NE47-321, Cambridge, MA 02139 USA

[8] Singapore MIT Alliance Res & Technol SMART, BioSyst & Micromech BioSyM, Singapore 138602, Singapore

来源：

ADVANCED SCIENCE | 2019年 / 6卷 / 20期

关键词：

3D Alzheimer's disease model; Alzheimer's disease; blood-brain barrier; VASCULAR OXIDATIVE STRESS; ENDOTHELIAL-CELLS; MATRIX METALLOPROTEINASES; NITRIC-OXIDE; ADULT BRAIN; IFN-GAMMA; PERMEABILITY; EXPRESSION; INCREASES; INTEGRITY;

D O I：

10.1002/advs.201900962

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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 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.

引用

页数：10

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