scholarly journals Cell-Culture Models of the Blood–Brain Barrier

Stroke ◽  
2014 ◽  
Vol 45 (8) ◽  
pp. 2514-2526 ◽  
Author(s):  
Yarong He ◽  
Yao Yao ◽  
Stella E. Tsirka ◽  
Yu Cao
Keyword(s):  
Cell Culture ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models

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.

Validation of in vitro cell culture models of the blood–brain barrier: Tightness characterization of two promising cell lines

2008 ◽  
Vol 97 (12) ◽  
pp. 5158-5175 ◽  
Author(s):  
Winfried Neuhaus ◽  
Verena E. Plattner ◽  
Michael Wirth ◽  
Bettina Germann ◽  
Bodo Lachmann ◽  
...  
Keyword(s):  
Cell Culture ◽  
Blood Brain Barrier ◽  
Cell Lines ◽  
Brain Barrier ◽  
In Vitro Cell Culture ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models

The role of aquaporin-4 in the blood–brain barrier development and integrity: Studies in animal and cell culture models

Neuroscience ◽  
2004 ◽  
Vol 129 (4) ◽  
pp. 935-944 ◽  
Author(s):  
G.P. Nicchia ◽  
B. Nico ◽  
L.M.A. Camassa ◽  
M.G. Mola ◽  
N. Loh ◽  
...  
Keyword(s):  
Cell Culture ◽  
Blood Brain Barrier ◽  
Aquaporin 4 ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models

scholarly journals Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1484
Author(s):  
Daisuke Watanabe ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Andrea E. Tóth ◽  
Monika Vastag ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Systems ◽  
Brain Endothelial Cells ◽  
Monkey Brain ◽  
Blood Brain ◽  
Culture Model ◽  
Culture Models ◽  
Human Primate

Culture models of the blood-brain barrier (BBB) are important research tools. Their role in the preclinical phase of drug development to estimate the permeability for potential neuropharmaceuticals is especially relevant. Since species differences in BBB transport systems exist, primate models are considered as predictive for drug transport to brain in humans. Based on our previous expertise we have developed and characterized a non-human primate co-culture BBB model using primary cultures of monkey brain endothelial cells, rat brain pericytes, and rat astrocytes. Monkey brain endothelial cells in the presence of both pericytes and astrocytes (EPA model) expressed enhanced barrier properties and increased levels of tight junction proteins occludin, claudin-5, and ZO-1. Co-culture conditions also elevated the expression of key BBB influx and efflux transporters, including glucose transporter-1, MFSD2A, ABCB1, and ABCG2. The correlation between the endothelial permeability coefficients of 10 well known drugs was higher (R2 = 0.8788) when the monkey and rat BBB culture models were compared than when the monkey culture model was compared to mouse in vivo data (R2 = 0.6619), hinting at transporter differences. The applicability of the new non-human primate model in drug discovery has been proven in several studies.

scholarly journals Effects of fasudil on blood-brain barrier integrity

2021 ◽  
Author(s):  
Kei Sato ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Yuki Matsunaga ◽  
Takashi Fujimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Tight Junction ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Tight Junction Protein ◽  
Brain Barrier ◽  
Blood Brain ◽  
Junction Protein ◽  
Culture Models

Abstract Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Medhods: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6-hour OGD/24-hour reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using immunohistochemistry and western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3–30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.

Permeability of PEGylated Immunoarsonoliposomes Through In Vitro Blood Brain Barrier-Medulloblastoma Co-culture Models for Brain Tumor Therapy

2014 ◽  
Vol 32 (3) ◽  
pp. 1072-1083 ◽  
Author(s):  
Abdulghani Al-Shehri ◽  
Marco E. Favretto ◽  
Panayiotis V. Ioannou ◽  
Ignacio A. Romero ◽  
Pierre-Olivier Couraud ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Blood Brain Barrier ◽  
Tumor Therapy ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Brain Tumor Therapy

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.

A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model

Small Methods ◽  
2021 ◽  
pp. 2100592
Author(s):  
Kaixiang Huang ◽  
Andre D. Castiaux ◽  
Ram Podicheti ◽  
Douglas B. Rusch ◽  
R. Scott Martin ◽  
...  
Keyword(s):  
Cell Culture ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Hybrid Nanofiber ◽  
Barrier Model
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