Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology

Hansang Cho, Ji Hae Seo, Keith H K Wong, Yasukazu Terasaki, Joseph Park, Ki Wan Bong, Ken Arai, Eng H. Lo, Daniel Irimia

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.

Original languageEnglish
Article number15222
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015 Oct 27
Externally publishedYes

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Blood-Brain Barrier
Pathology
Adherens Junctions
In Vitro Techniques
Inflammation Mediators
Microfluidics
Tight Junctions
Chemotactic Factors
Drug Delivery Systems
Coloring Agents
Endothelial Cells
Animal Models
Antioxidants
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology. / Cho, Hansang; Seo, Ji Hae; Wong, Keith H K; Terasaki, Yasukazu; Park, Joseph; Bong, Ki Wan; Arai, Ken; Lo, Eng H.; Irimia, Daniel.

In: Scientific Reports, Vol. 5, 15222, 27.10.2015.

Research output: Contribution to journalArticle

Cho, H, Seo, JH, Wong, KHK, Terasaki, Y, Park, J, Bong, KW, Arai, K, Lo, EH & Irimia, D 2015, 'Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology', Scientific Reports, vol. 5, 15222. https://doi.org/10.1038/srep15222
Cho, Hansang ; Seo, Ji Hae ; Wong, Keith H K ; Terasaki, Yasukazu ; Park, Joseph ; Bong, Ki Wan ; Arai, Ken ; Lo, Eng H. ; Irimia, Daniel. / Three-dimensional blood-brain barrier model for in vitro studies of neurovascular pathology. In: Scientific Reports. 2015 ; Vol. 5.
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