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.
Bibliographical noteFunding Information:
All microfabrication procedures were performed at the BioMEMS Resource Center, supported by National Institutes of Health grant EB002503 and National Institute of Neurological Disorders and Stroke grant NS045776. Dr. Didier Dréau lab at UNC Charlotte provided access to equipment for running a hypoxia experiment and reading cytokine membrane. We gratefully acknowledge the support of National Institutes of Health grant GM092804 and CRI (Charlotte Research Institute) Duke Energy Special Initiatives Funding.
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