dc.contributor.author | Boghdeh, Niloufar A. | |
dc.contributor.author | Risner, Kenneth H. | |
dc.contributor.author | Barrera, Michael D. | |
dc.contributor.author | Britt, Clayton M. | |
dc.contributor.author | Schaffer, David K. | |
dc.contributor.author | Alem, Farhang | |
dc.contributor.author | Brown, Jacquelyn A. | |
dc.contributor.author | Wikswo, John P. | |
dc.contributor.author | Narayanan, Aarthi | |
dc.date.accessioned | 2023-01-24T19:43:48Z | |
dc.date.available | 2023-01-24T19:43:48Z | |
dc.date.issued | 2022-12-15 | |
dc.identifier.citation | Boghdeh, N.A.; Risner, K.H.; Barrera, M.D.; Britt, C.M.; Schaffer, D.K.; Alem, F.; Brown, J.A.; Wikswo, J.P.; Narayanan, A. Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus. Viruses 2022, 14, 2799. https://doi.org/ 10.3390/v14122799 | en_US |
dc.identifier.other | eISSN 1999-4915 | |
dc.identifier.other | PubMed ID36560802 | |
dc.identifier.uri | http://hdl.handle.net/1803/17941 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | The research was supported by a grant awarded by the Defense Threat Reduction Agency
for AN (HDTRA11810040 and HDTRA1-23-1-0003) and by funding provided to JW by the National
Center for Advancing Translational Sciences of the National Institutes of Health under Award Number
UH3TR002097. The content is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Viruses-basel | en_US |
dc.rights | © 2022 by the authors.
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/). | |
dc.source.uri | https://mdpi-res.com/viruses/viruses-14-02799/article_deploy/viruses-14-02799.pdf?version=1671096225 | |
dc.subject | Venezuelan Equine Encephalitis Virus | en_US |
dc.subject | alphaviruses | en_US |
dc.subject | neurovascular unit (NVU) | en_US |
dc.subject | organ-on-a-chip | en_US |
dc.subject | blood brain barrier | en_US |
dc.subject | omaveloxolone | en_US |
dc.subject | RTA408 | en_US |
dc.title | Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.3390/v14122799 | |