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In Vitro Cerebrovascular Modeling in the 21st Century: Current and Prospective Technologies

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Abstract

The blood-brain barrier (BBB) maintains the brain homeostasis and dynamically responds to events associated with systemic and/or rheological impairments (e.g., inflammation, ischemia) including the exposure to harmful xenobiotics. Thus, understanding the BBB physiology is crucial for the resolution of major central nervous system CNS) disorders challenging both health care providers and the pharmaceutical industry. These challenges include drug delivery to the brain, neurological disorders, toxicological studies, and biodefense. Studies aimed at advancing our understanding of CNS diseases and promoting the development of more effective therapeutics are primarily performed in laboratory animals. However, there are major hindering factors inherent to in vivo studies such as cost, limited throughput and translational significance to humans. These factors promoted the development of alternative in vitro strategies for studying the physiology and pathophysiology of the BBB in relation to brain disorders as well as screening tools to aid in the development of novel CNS drugs. Herein, we provide a detailed review including pros and cons of current and prospective technologies for modelling the BBB in vitro including ex situ, cell based and computational (in silico) models. A special section is dedicated to microfluidic systems including micro-BBB, BBB-on-a-chip, Neurovascular Unit-on-a-Chip and Synthetic Microvasculature Blood-brain Barrier.

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by NIH/NIDA R01-DA029121-01A1 and Alternative Research Development Foundation (A.R.D.F.) to Dr. Luca Cucullo. The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA

    Shikha Prasad, Pooja Naik, Kaisar M. D. Abul, Ravi K. Sajja & Luca Cucullo

  2. Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA

    Luca Cucullo

  3. Draper Laboratory Bioengineering Center, Tampa, FL, 33612, USA

    Christopher A. Palmiotti & Anilkumar H. Achyuta

  4. School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX, 79106, USA

    Luca Cucullo

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  1. Christopher A. Palmiotti
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  2. Shikha Prasad
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  3. Pooja Naik
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  4. Kaisar M. D. Abul
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Correspondence to Luca Cucullo.

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Palmiotti, C.A., Prasad, S., Naik, P. et al. In Vitro Cerebrovascular Modeling in the 21st Century: Current and Prospective Technologies. Pharm Res 31, 3229–3250 (2014). https://doi.org/10.1007/s11095-014-1464-6

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