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Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus

The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of...

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Autores principales: Boghdeh, Niloufar A., Risner, Kenneth H., Barrera, Michael D., Britt, Clayton M., Schaffer, David K., Alem, Farhang, Brown, Jacquelyn A., Wikswo, John P., Narayanan, Aarthi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786295/
https://www.ncbi.nlm.nih.gov/pubmed/36560802
http://dx.doi.org/10.3390/v14122799
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author Boghdeh, Niloufar A.
Risner, Kenneth H.
Barrera, Michael D.
Britt, Clayton M.
Schaffer, David K.
Alem, Farhang
Brown, Jacquelyn A.
Wikswo, John P.
Narayanan, Aarthi
author_facet Boghdeh, Niloufar A.
Risner, Kenneth H.
Barrera, Michael D.
Britt, Clayton M.
Schaffer, David K.
Alem, Farhang
Brown, Jacquelyn A.
Wikswo, John P.
Narayanan, Aarthi
author_sort Boghdeh, Niloufar A.
collection PubMed
description The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load.
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spelling pubmed-97862952022-12-24 Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus Boghdeh, Niloufar A. Risner, Kenneth H. Barrera, Michael D. Britt, Clayton M. Schaffer, David K. Alem, Farhang Brown, Jacquelyn A. Wikswo, John P. Narayanan, Aarthi Viruses Article The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load. MDPI 2022-12-15 /pmc/articles/PMC9786295/ /pubmed/36560802 http://dx.doi.org/10.3390/v14122799 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boghdeh, Niloufar A.
Risner, Kenneth H.
Barrera, Michael D.
Britt, Clayton M.
Schaffer, David K.
Alem, Farhang
Brown, Jacquelyn A.
Wikswo, John P.
Narayanan, Aarthi
Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title_full Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title_fullStr Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title_full_unstemmed Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title_short Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus
title_sort application of a human blood brain barrier organ-on-a-chip model to evaluate small molecule effectiveness against venezuelan equine encephalitis virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786295/
https://www.ncbi.nlm.nih.gov/pubmed/36560802
http://dx.doi.org/10.3390/v14122799
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