Transport Studies Using Blood-Brain Barrier In Vitro Models: A Critical Review and Guidelines

Endothelial cells exposed to inductive central nervous system factors differentiate into a blood-brain barrier phenotype. The blood-brain barrier frequently obstructs the passage of chemotherapeutics into the brain. Tissue culture systems have been developed to reproduce key properties of the intact blood-brain barrier and to allow for testing of mechanisms of transendothelial drug permeation.

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In vitro models of the blood-brain barrier to study bacterial meningitis

Trends in Microbiology ◽

10.1016/s0966-842x(00)88999-4 ◽

1995 ◽

Vol 3 (11) ◽

pp. 441-445 ◽

Cited By ~ 6

Author(s):

G Townsend

Keyword(s):

Bacterial Meningitis ◽

Blood Brain Barrier ◽

In Vitro Models ◽

Brain Barrier ◽

Blood Brain

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Human induced pluripotent stem cell based in vitro models of the blood-brain barrier: the future standard?

Neural Regeneration Research ◽

10.4103/1673-5374.217326 ◽

2017 ◽

Vol 12 (10) ◽

pp. 1607 ◽

Cited By ~ 4

Author(s):

Winfried Neuhaus

Keyword(s):

Stem Cell ◽

Blood Brain Barrier ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

In Vitro Models ◽

Brain Barrier ◽

Blood Brain ◽

The Future ◽

Induced Pluripotent

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Claudin-5 Expression in In Vitro Models of the Blood–Brain Barrier

Methods in Molecular Biology - Claudins ◽

10.1007/978-1-61779-185-7_25 ◽

2011 ◽

pp. 347-354 ◽

Cited By ~ 15

Author(s):

Itzik Cooper ◽

Katayun Cohen-Kashi-Malina ◽

Vivian I. Teichberg

Keyword(s):

Blood Brain Barrier ◽

In Vitro Models ◽

Brain Barrier ◽

Blood Brain

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Hurdles with Using In Vitro Models to Predict Human Blood-brain Barrier Drug Permeability: A Special Focus on Transporters and Metabolizing Enzymes

Current Drug Metabolism ◽

10.2174/1389200211309010120 ◽

2012 ◽

Vol 14 (1) ◽

pp. 120-136 ◽

Cited By ~ 1

Author(s):

Ramzi Shawahna ◽

Xavier Decleves ◽

Jean-Michel Scherrmann

Keyword(s):

Blood Brain Barrier ◽

Human Blood ◽

In Vitro Models ◽

Brain Barrier ◽

Special Focus ◽

Metabolizing Enzymes ◽

Drug Permeability ◽

Blood Brain

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Mechanisms of Glutamate Efflux at the Blood—Brain Barrier: Involvement of Glial Cells

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.121 ◽

2011 ◽

Vol 32 (1) ◽

pp. 177-189 ◽

Cited By ~ 34

Author(s):

Katayun Cohen-Kashi-Malina ◽

Itzik Cooper ◽

Vivian I Teichberg

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Glial Cells ◽

Excitatory Amino Acid ◽

Active Role ◽

In Vitro Models ◽

Brain Barrier ◽

Amino Acid Transporters ◽

Blood Brain

At high concentrations, glutamate (Glu) exerts potent neurotoxic properties, leading to irreversible brain damages found in numerous neurological disorders. The accepted notion that Glu homeostasis in brain interstitial fluid is maintained primarily through the activity of Glu transporters present on glial cells does not take into account the possible contribution of endothelial cells constituting the blood-brain barrier (BBB) to this process. Here, we present evidence for the presence of the Glu transporters, excitatory amino-acid transporters (EAATs) 1 to 3, in porcine brain endothelial cells (PBECs) and show their participation in Glu uptake into PBECs. Moreover, transport of Glu across three in vitro models of the BBB is investigated for the first time, and evidence for Glu transport across the BBB in both directions is presented. Our results provide evidence that the BBB can function in the efflux mode to selectively remove Glu, via specific transporters, from the abluminal side (brain) into the luminal compartment (blood). Furthermore, we found that glial cells lining the BBB have an active role in the efflux process by taking up Glu and releasing it, through hemichannels, anion channels, and possibly the reversal of its EAATs, in close proximity to ECs, which in turn take up Glu and release it to the blood.

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