scholarly journals An In Vitro Model of the Blood-brain Barrier Using Impedance Spectroscopy: A Focus on T Cell-endothelial Cell Interaction

10.3791/54592 ◽  
2016 ◽  
Author(s):  
Ivan Kuzmanov ◽  
Alexander M. Herrmann ◽  
Hans-Joachim Galla ◽  
Sven G. Meuth ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
T Cell ◽  
Impedance Spectroscopy ◽  
Blood Brain Barrier ◽  
Cell Interaction ◽  
Brain Barrier ◽  
Endothelial Cell Interaction ◽  
Blood Brain

scholarly journals In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

2016 ◽  
Vol 36 (5) ◽  
pp. 862-890 ◽  
Author(s):  
Hans C Helms ◽  
N Joan Abbott ◽  
Malgorzata Burek ◽  
Romeo Cecchelli ◽  
Pierre-Olivier Couraud ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models ◽  
The Brain

The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described.

scholarly journals CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport

2020 ◽  
Vol 9 (10) ◽  
pp. 3236
Author(s):  
Luke Wainwright ◽  
Iain P. Hargreaves ◽  
Ana R. Georgian ◽  
Charles Turner ◽  
R. Neil Dalton ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Advanced Glycation Endproducts ◽  
Brain Barrier ◽  
High Dose ◽  
Blood Brain ◽  
Coq10 Deficiency ◽  
The Brain

Primary coenzyme Q10 (CoQ10) deficiency is unique among mitochondrial respiratory chain disorders in that it is potentially treatable if high-dose CoQ10 supplements are given in the early stages of the disease. While supplements improve peripheral abnormalities, neurological symptoms are only partially or temporarily ameliorated. The reasons for this refractory response to CoQ10 supplementation are unclear, however, a contributory factor may be the poor transfer of CoQ10 across the blood–brain barrier (BBB). The aim of this study was to investigate mechanisms of CoQ10 transport across the BBB, using normal and pathophysiological (CoQ10 deficient) cell culture models. The study identifies lipoprotein-associated CoQ10 transcytosis in both directions across the in vitro BBB. Uptake via SR-B1 (Scavenger Receptor) and RAGE (Receptor for Advanced Glycation Endproducts), is matched by efflux via LDLR (Low Density Lipoprotein Receptor) transporters, resulting in no “net” transport across the BBB. In the CoQ10 deficient model, BBB tight junctions were disrupted and CoQ10 “net” transport to the brain side increased. The addition of anti-oxidants did not improve CoQ10 uptake to the brain side. This study is the first to generate in vitro BBB endothelial cell models of CoQ10 deficiency, and the first to identify lipoprotein-associated uptake and efflux mechanisms regulating CoQ10 distribution across the BBB. The results imply that the uptake of exogenous CoQ10 into the brain might be improved by the administration of LDLR inhibitors, or by interventions to stimulate luminal activity of SR-B1 transporters.

Immortalized endothelial cell lines for in vitro blood–brain barrier models: A systematic review

2016 ◽  
Vol 1642 ◽  
pp. 532-545 ◽  
Author(s):  
Nurul Adhwa Rahman ◽  
Alifah Nur’ain Haji Mat Rasil ◽  
Uta Meyding-Lamade ◽  
Eva Maria Craemer ◽  
Suwarni Diah ◽  
...  
Keyword(s):  
Systematic Review ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Cell Lines ◽  
Brain Barrier ◽  
Blood Brain

Development of immortalized human cerebromicrovascular endothelial cell line as an in vitro model of the human blood–brain barrier

1997 ◽  
Vol 11 (13) ◽  
pp. 1187-1197 ◽  
Author(s):  
Arumugam Muruganandam ◽  
Leonie Moorhouse Herx ◽  
Robert Monette ◽  
Jon P. Durkin ◽  
Danica B. Stanimirovic
Keyword(s):  
Endothelial Cell ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Human Blood ◽  
In Vitro Model ◽  
Brain Barrier ◽  
Endothelial Cell Line ◽  
Blood Brain ◽  
Vitro Model

scholarly journals 3D brain angiogenesis model to reconstitute maturation of functional human blood-brain barrier in vitro

2018 ◽  
Author(s):  
Somin Lee ◽  
Minhwan Chung ◽  
Noo Li Jeon
Keyword(s):  
Blood Brain Barrier ◽  
Developmental Process ◽  
Cell Interaction ◽  
Brain Barrier ◽  
Perivascular Cells ◽  
Perivascular Cell ◽  
Blood Brain ◽  
Hydrogel Matrix ◽  
Characteristic Features

0.AbstractHuman central nervous system (CNS) vasculature in brain expresses a distinctive barrier phenotype, the blood–brain barrier (BBB), which protects the brain against harmful pathogens. Since the BBB contributes to low success rate in CNS pharmacotherapy by restricting drug transportation, the development of an in vitro human BBB model has been in demand. Previous models were unable to fully represent the complex threedimensional (3D) anatomical structure or specific barrier phenotypes of the matured BBB. In this study, we present a physiological 3D microfluidic model of the human BBB that mimics its developmental process including CNS angiogenesis and subsequent maturation in concert with perivascular cells. We used microfluidic hydrogel patterning to precisely and sequentially load perivascular cells into the model, investigate the role of each cell type on BBB phenotypes. We confirmed the necessity of the tri-culture system (brain endothelium with pericytes and astrocytes) to attain the characteristic BBB vascular morphology such as minimized diameter and maximized junction expression. In addition, endothelial-perivascular cell interaction was also critical in reconstituting p-glycoprotein (p-gp), efflux transporter in our model that works as metabolic barrier of BBB and blocks drug to enter CNS. The 3D hydrogel matrix was tuned with hyaluronic acid (HA) to optimize the interaction between endothelial cells and astrocytes. Our in vitro BBB system mimics CNS angiogenesis and characteristic features of BBB. We expect the model will contribute to deeper understanding of neurodegenerative diseases and cost-efficient development of effective CNS medications.

scholarly journals Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier

2021 ◽  
Vol 134 (8) ◽  
Author(s):  
Mariana Castro Dias ◽  
Adolfo Odriozola Quesada ◽  
Sasha Soldati ◽  
Fabio Bösch ◽  
Isabelle Gruber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Blood Brain Barrier ◽  
Immune Surveillance ◽  
Brain Barrier ◽  
Activated T Cells ◽  
Blood Brain ◽  
Primary Mouse ◽  
Underlying Mechanisms

ABSTRACT The migration of activated T cells across the blood–brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper.

scholarly journals The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model

nano Online ◽  
2016 ◽  
Author(s):  
Malka Shilo ◽  
Anat Sharon ◽  
Koby Baranes ◽  
Menachem Motiei ◽  
Jean-Paul M Lellouche ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Cell Model ◽  
Brain Barrier ◽  
Nanoparticle Size ◽  
Blood Brain

scholarly journals Yuzu and Hesperidin Ameliorate Blood-Brain Barrier Disruption during Hypoxia via Antioxidant Activity

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 843
Author(s):  
Bo Kyung Lee ◽  
Soo-Wang Hyun ◽  
Yi-Sook Jung
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Brain Barrier ◽  
Blood Brain ◽  
In Vivo Animal Model ◽  
Bbb Permeability

Yuzu and its main component, hesperidin (HSP), have several health benefits owing to their anti-inflammatory and antioxidant properties. We examined the effects of yuzu and HSP on blood–brain barrier (BBB) dysfunction during ischemia/hypoxia in an in vivo animal model and an in vitro BBB endothelial cell model, and also investigated the underlying mechanisms. In an in vitro BBB endothelial cell model, BBB permeability was determined by measurement of Evans blue extravasation in vivo and in vitro. The expression of tight junction proteins, such as claudin-5 and zonula occludens-1 (ZO-1), was detected by immunochemistry and western blotting, and the reactive oxygen species (ROS) level was measured by 2′7′-dichlorofluorescein diacetate intensity. Yuzu and HSP significantly ameliorated the increase in BBB permeability and the disruption of claudin-5 and ZO-1 in both in vivo and in vitro models. In bEnd.3 cells, yuzu and HSP were shown to inhibit the disruption of claudin-5 and ZO-1 during hypoxia, and the protective effects of yuzu and HSP on claudin-5 degradation seemed to be mediated by Forkhead box O 3a (FoxO3a) and matrix metalloproteinase (MMP)-3/9. In addition, well-known antioxidants, trolox and N-acetyl cysteine, significantly attenuated the BBB permeability increase, disruption of claudin-5 and ZO-1, and FoxO3a activation during hypoxia, suggesting that ROS are important mediators of BBB dysfunction during hypoxia. Collectively, these results indicate that yuzu and HSP protect the BBB against dysfunction via maintaining integrity of claudin-5 and ZO-1, and these effects of yuzu and HSP appear to be a facet of their antioxidant properties. Our findings may contribute to therapeutic strategies for BBB-associated neurodegenerative diseases.

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