scholarly journals Online Measurement System for Dynamic Flow Bioreactors to Study Barrier Integrity of hiPSC-Based Blood–Brain Barrier In Vitro Models

2022 ◽  
Vol 9 (1) ◽  
pp. 39
Author(s):  
Jihyoung Choi ◽  
Sanjana Mathew ◽  
Sabrina Oerter ◽  
Antje Appelt-Menzel ◽  
Jan Hansmann ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Non Invasive ◽  
Dynamic Culture ◽  
Blood Brain ◽  
Bioreactor System ◽  
Static Conditions

Electrochemical impedance spectroscopy (EIS) is a noninvasive, reliable, and efficient method to analyze the barrier integrity of in vitro tissue models. This well-established tool is used most widely to quantify the transendothelial/epithelial resistance (TEER) of Transwell-based models cultured under static conditions. However, dynamic culture in bioreactors can achieve advanced cell culture conditions that mimic a more tissue-specific environment and stimulation. This requires the development of culture systems that also allow for the assessment of barrier integrity under dynamic conditions. Here, we present a bioreactor system that is capable of the automated, continuous, and non-invasive online monitoring of cellular barrier integrity during dynamic culture. Polydimethylsiloxane (PDMS) casting and 3D printing were used for the fabrication of the bioreactors. Additionally, attachable electrodes based on titanium nitride (TiN)-coated steel tubes were developed to perform EIS measurements. In order to test the monitored bioreactor system, blood–brain barrier (BBB) in vitro models derived from human-induced pluripotent stem cells (hiPSC) were cultured for up to 7 days. We applied equivalent electrical circuit fitting to quantify the electrical parameters of the cell layer and observed that TEER gradually decreased over time from 2513 Ω·cm2 to 285 Ω·cm2, as also specified in the static control culture. Our versatile system offers the possibility to be used for various dynamic tissue cultures that require a non-invasive monitoring system for barrier integrity.

scholarly journals Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models

2021 ◽  
Vol 1 (5) ◽  
pp. 2170051
Author(s):  
Christina L. Schofield ◽  
Aleixandre Rodrigo-Navarro ◽  
Matthew J. Dalby ◽  
Tom Van Agtmael ◽  
Manuel Salmeron-Sanchez
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain

Understanding the Physiology of the Blood-Brain Barrier: In Vitro Models

Physiology ◽  
1998 ◽  
Vol 13 (6) ◽  
pp. 287-293 ◽  
Author(s):  
Gerald A. Grant ◽  
N. Joan Abbott ◽  
Damir Janigro
Keyword(s):  
Central Nervous System ◽  
Tissue Culture ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain ◽  
Brain Tissue Culture ◽  
The Brain

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.

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

2011 ◽  
pp. 347-354 ◽  
Author(s):  
Itzik Cooper ◽  
Katayun Cohen-Kashi-Malina ◽  
Vivian I. Teichberg
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain

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

2020 ◽  
Author(s):  
Ana R. Santa-Maria ◽  
Marjolein Heymans ◽  
Fruzsina R. Walter ◽  
Maxime Culot ◽  
Fabien Gosselet ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Critical Review ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Transport Studies ◽  
Blood Brain

scholarly journals Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship withCYP2B6c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

2016 ◽  
Vol 60 (8) ◽  
pp. 4511-4518 ◽  
Author(s):  
Sam Nightingale ◽  
Tran Thi Hong Chau ◽  
Martin Fisher ◽  
Mark Nelson ◽  
Alan Winston ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Toxic Concentration ◽  
Metabolite Concentrations ◽  
Blood Brain Barrier Integrity

ABSTRACTEfavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxinin vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available publishedin vitroandin vivodata. The effect of theCYP2B6c.516G→T genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above thein vitrotoxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above thein vitrotoxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of theCYP2B6genotype, particularly in those with impaired blood-brain barrier integrity.

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

2011 ◽  
Vol 32 (1) ◽  
pp. 177-189 ◽  
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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