Cell-based in vitro models for studying blood–brain barrier (BBB) permeability

2016 ◽  
pp. 169-188 ◽  
Author(s):  
Maria João Gomes ◽  
Bárbara Mendes ◽  
Susana Martins ◽  
Bruno Sarmento
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability

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

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

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 Sleep Deprivation Induces Cognitive Impairment by Increasing Blood-Brain Barrier Permeability via CD44

2020 ◽  
Vol 11 ◽  
Author(s):  
Jing Sun ◽  
Jusheng Wu ◽  
Fuzhou Hua ◽  
Yong Chen ◽  
Fenfang Zhan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Sleep Deprivation ◽  
Rna Sequencing ◽  
Blood Brain Barrier ◽  
Nervous System Development ◽  
Brain Barrier ◽  
Receptor Interaction ◽  
Blood Brain ◽  
Bbb Permeability

Sleep deprivation occurs frequently in older adults, which can result in delirium and cognitive impairment. CD44 is a key molecular in blood-brain barrier (BBB) regulation. However, whether CD44 participates in the role of sleep deprivation in cognitive impairment remains unclear. In this study, the effect of sleep deprivation on cognitive ability, tissue inflammation, BBB permeability, and astrocyte activity were evaluated in vivo. The differentially expressed genes (DEGs) were identified by RNA sequencing. A CD44 overexpression in the BBB model was performed in vitro to assess the effect and mechanisms of CD44. Sleep deprivation impaired the learning and memory ability and increased the levels of inflammatory cytokines, along with increased BBB permeability and activated astrocytes in hippocampus tissue. RNA sequencing of the hippocampus tissue revealed that 329 genes were upregulated in sleep deprivation-induced mice compared to control mice, and 147 genes were downregulated. GO and pathways showed that DEGs were mainly involved in BBB permeability and astrocyte activation, including nervous system development, neuron development, and brain development, and neuroactive ligand-receptor interaction. Moreover, the PCR analysis revealed that CD44 was dramatically increased in mice with sleep deprivation induction. The overexpression of CD44 in astrocytes promoted BBB permeability in vitro and induced the expression of the downstream gene NANOG. Our results indicate that sleep deprivation upregulated CD44 expression in hippocampus tissue, and increased BBB permeability, resulting in cognitive impairment.

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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