Biology and Models of the Blood–Brain Barrier

The blood–brain barrier (BBB) is one of the most selective endothelial barriers. An understanding of its cellular, morphological, and biological properties in health and disease is necessary to develop therapeutics that can be transported from blood to brain. In vivo models have provided some insight into these features and transport mechanisms adopted at the brain, yet they have failed as a robust platform for the translation of results into clinical outcomes. In this article, we provide a general overview of major BBB features and describe various models that have been designed to replicate this barrier and neurological pathologies linked with the BBB. We propose several key parameters and design characteristics that can be employed to engineer physiologically relevant models of the blood–brain interface and highlight the need for a consensus in the measurement of fundamental properties of this barrier.

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Drug Transfer Across the Blood-Brain Barrier: Comparison of in Vitro and in Vivo Models

Frontiers in Cerebral Vascular Biology - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-2920-0_18 ◽

1993 ◽

pp. 113-115 ◽

Cited By ~ 7

Author(s):

C. Chesné ◽

M. P. Dehouck ◽

P. Jolliet-Riant ◽

F. Brée ◽

J. P. Tillement ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

In Vivo Models ◽

Drug Transfer ◽

Blood Brain

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Drug Transfer Across the Blood-Brain Barrier: Correlation Between in Vitro and in Vivo Models

Vascular Endothelium ◽

10.1007/978-1-4615-2437-3_21 ◽

1993 ◽

pp. 161-161

Author(s):

M. P. Dehouck ◽

B. Dehouck ◽

J. C. Fruchart ◽

R. Cecchelli ◽

P. Jolliet-Riant ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

In Vivo Models ◽

Drug Transfer ◽

Blood Brain

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miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.154 ◽

2015 ◽

Vol 35 (12) ◽

pp. 1957-1965 ◽

Cited By ~ 54

Author(s):

Slava Rom ◽

Holly Dykstra ◽

Viviana Zuluaga-Ramirez ◽

Nancy L Reichenbach ◽

Yuri Persidsky

Keyword(s):

Blood Brain Barrier ◽

Glycogen Synthase ◽

Leukocyte Adhesion ◽

Brain Barrier ◽

Brain Endothelium ◽

In Vivo Models ◽

Blood Brain ◽

Microarray Screening

Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier ‘leakiness’ in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.

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