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In Vitro Cell Models of the Human Blood-Brain Barrier: Demonstrating the Beneficial Influence of Shear Stress on Brain Microvascular Endothelial Cell Phenotype

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Blood-Brain Barrier

Part of the book series: Neuromethods ((NM,volume 142))

Abstract

The field of translational cerebrovascular research routinely employs blood-brain barrier (BBB) cell models. Using in vitro culture models to accurately mimic the physiological complexity of the in vivo BBB continues to be a challenge, however. To meet this challenge, in vitro BBB models have evolved significantly over the last three decades, from static monocultures to dynamic multicellular flow-based systems. In this chapter, we initially focus on three key aspects that have helped to drive the evolution of in vitro BBB models, namely (1) the availability of suitable BBB cell lines; (2) a fuller understanding of the neurovascular unit (NVU); and (3) an appreciation of the relevance of blood flow shear stress to BBB physiology. We then put this knowledge into a more practical context by experimentally demonstrating two alternate means of applying physiological shear stress to primary-derived human brain microvascular endothelial cells (HBMvECs), and showing how BBB phenotype is improved in response to flow by using immunocytochemical localization of tight-junction zonula occludens-1 (ZO-1) as a reporter index. The ability of applied shear to attenuate the pro-oxidant effects of inflammatory TNF-α in HBMvECs will also be demonstrated using flow cytometry, further highlighting the relevance of introducing shear into BBB models.

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Acknowledgments

The authors are grateful for financial support from the National Development Plan/Higher Education Authority of Ireland Programme for Research in Third Level Institutes (HEA/PRTLI Cycle 4—T3 Targeted Therapeutics and Theranostics) and from Science Foundation Ireland (US-Ireland R&D Partnership Programme, Grant No. 14/US/B3116).

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  1. School of Biotechnology, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland

    Keith D. Rochfort & Philip M. Cummins

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Correspondence to Keith D. Rochfort .

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  1. Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Tatiana Barichello

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Rochfort, K.D., Cummins, P.M. (2019). In Vitro Cell Models of the Human Blood-Brain Barrier: Demonstrating the Beneficial Influence of Shear Stress on Brain Microvascular Endothelial Cell Phenotype. In: Barichello, T. (eds) Blood-Brain Barrier. Neuromethods, vol 142. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8946-1_5

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