Simulating the blood-brain barrier by using artificial membranes, multicellular culturing systems, and high-tech applications

Abstract

Background: The blood-brain barrier (BBB) is an intricate structure of the vascular endothelium that regulates trafficking required for cerebral homeostasis via tightly regulated influx and efflux transport mechanisms. It also performs a critical function in mediating communication between the periphery and the central nervous system (CNS). The BBB is designed to maintain a precisely regulated microenvironment conducive to normal neuronal activity. The development of in vitro BBB models has been driven by the need for a fast, reliable, and cost-effective tool to study the complexities of the BBB and to screen potential CNS drugs. Aim: This review provides readers with a concise yet comprehensive introduction to the fundamental histology of the BBB. This background is essential for interpreting model design constraints and limitations in BBB simulation. Following that, we thoroughly examine in vitro models, providing a comprehensive analysis of their applications and the equations used to assess specific BBB parameters. Relevance for patients: From a translational and clinical perspective, in vitro models of the BBB have the potential to provide novel insights into brain pathophysiology under adverse conditions, including brain tumors, traumatic injuries, strokes, and neurodegenerative disorders, and ultimately aid in the discovery of effective treatment strategies.

Keywords

Blood-brain barrier / In vitro blood-brain barrier models / Integrity assays / Neurovascular unit

Acknowledgments

We would like to express our gratitude to the Department of Industrial and Environmental Biotechnology at NIGEB.

Funding

Michael J. Strong receives funding from the Canadian Institutes of Health Research (SOP-160442) and the Temerty Family Foundation.

Conflict of interest

The authors declare they have no competing interests.

Author contributions

Conceptualization: Hamdam Hourfar, Farhang Aliakbari, Daniel E. Otzen, Michael J. Strong, Dina Morshedi Visualization: Arghavan Fattahi Writing – original draft: Hamdam Hourfar, Arghavan Fattahi, Mohammad Raeiji, Kimia Marzookian, Naser Safari, Narges Nasrollahi Boroujeni Writing – review & editing: Hamdam Hourfar, Farhang Aliakbari, Daniel E. Otzen, Michael J. Strong, Dina Morshedi

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Not applicable.

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