scholarly journals Gene Expression Changes in Long-Term In Vitro Human Blood-Brain Barrier Models and Their Dependence on a Transwell Scaffold Material

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Joel D. Gaston ◽  
Lauren L. Bischel ◽  
Lisa A. Fitzgerald ◽  
Kathleen D. Cusick ◽  
Bradley R. Ringeisen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Brain Barrier ◽  
Disease Modeling ◽  
Brain Barrier ◽  
Cell Contact ◽  
Normal Brain ◽  
Scaffold Material ◽  
Blood Brain ◽  
Coculture Model

Disruption of the blood-brain barrier (BBB) is the hallmark of many neurovascular disorders, making it a critically important focus for therapeutic options. However, testing the effects of either drugs or pathological agents is difficult due to the potentially damaging consequences of altering the normal brain microenvironment. Recently, in vitro coculture tissue models have been developed as an alternative to animal testing. Despite low cost, these platforms use synthetic scaffolds which prevent normal barrier architecture, cellular crosstalk, and tissue remodeling. We created a biodegradable electrospun gelatin mat “biopaper” (BP) as a scaffold material for an endothelial/astrocyte coculture model allowing cell-cell contact and crosstalk. To compare the BP and traditional models, we investigated the expression of 27 genes involved in BBB permeability, cellular function, and endothelial junctions at different time points. Gene expression levels demonstrated higher expression of transcripts involved in endothelial junction formation, including TJP2 and CDH5, in the BP model. The traditional model had higher expression of genes associated with extracellular matrix-associated proteins, including SPARC and COL4A1. Overall, the results demonstrate that the BP coculture model is more representative of a healthy BBB state, though both models have advantages that may be useful in disease modeling.

scholarly journals Metabolic Acidosis Induced by Plasmodium Falciparum Intraerythrocytic Stages Alters Blood—Brain Barrier Integrity

2010 ◽  
Vol 31 (2) ◽  
pp. 514-526 ◽  
Author(s):  
Sergine Zougbédé ◽  
Florence Miller ◽  
Philippe Ravassard ◽  
Angelita Rebollo ◽  
Liliane Cicéron ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Metabolic Acidosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Microvascular Endothelial Cell ◽  
Blood Brain ◽  
Coculture Model ◽  
Antiparasitic Drugs ◽  
Permeability Increase

The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood–brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs.

scholarly journals Three-dimensional microenvironment regulates gene expression, function, and tight junction dynamics of iPSC-derived blood-brain barrier microvessels

2021 ◽  
Author(s):  
Raleigh M. Linville ◽  
Matthew B. Sklar ◽  
Gabrielle N. Grifno ◽  
Renee F. Nerenberg ◽  
Justin Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Three Dimensional ◽  
Brain Barrier ◽  
Time Dynamics ◽  
Blood Brain ◽  
Wide Range ◽  
3D Microenvironment

The blood-brain barrier (BBB) plays a pivotal role in brain health and disease. In the BBB, brain microvascular endothelial cells (BMECs) are connected by tight junctions which regulate paracellular transport, and express specialized transporter systems which regulate transcellular transport. However, existing in vitro models of the BBB display variable physiological accuracy across a wide range of characteristics including gene/protein expression and barrier function. Here, we use an isogenic family of fluorescently-labeled iPSC-derived BMEC-like cells (iBMECs) and brain pericyte-like cells (iPCs) within two-dimensional confluent monolayers (2D) and three-dimensional (3D) tissue-engineered microvessels to explore how 3D microenvironment regulates gene expression and function of the in vitro BBB. We show that 3D microenvironment (shear stress, cell-ECM interactions, and cylindrical geometry) increases BBB phenotype and endothelial identity, and alters angiogenic and cytokine responses in synergy with pericyte co-culture. Tissue-engineered microvessels incorporating junction-labeled iBMECs enable study of the real-time dynamics of tight junctions during homeostasis and in response to physical and chemical perturbations.

scholarly journals Cytotoxicity and apoptotic gene expression in an in vitro model of the blood–brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles

2016 ◽  
Vol 24 (7) ◽  
pp. 635-644 ◽  
Author(s):  
Andrew M. Hall ◽  
Ruth Hemmer ◽  
Robert Spaulding ◽  
Hanna N. Wetzel ◽  
Joseph Curcio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Brain Barrier ◽  
In Vitro Model ◽  
Brain Barrier ◽  
Apoptotic Gene ◽  
Blood Brain ◽  
Vitro Model
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