PMID- 36560802 OWN - NLM STAT- MEDLINE DCOM- 20221226 LR - 20230610 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 14 IP - 12 DP - 2022 Dec 15 TI - Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus. LID - 10.3390/v14122799 [doi] LID - 2799 AB - 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. FAU - Boghdeh, Niloufar A AU - Boghdeh NA AUID- ORCID: 0000-0002-2678-6481 AD - Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA. FAU - Risner, Kenneth H AU - Risner KH AUID- ORCID: 0000-0001-6999-7564 AD - Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA. AD - College of Science, School of Systems Biology, George Mason University, Manassas, VA 20110, USA. FAU - Barrera, Michael D AU - Barrera MD AD - Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA. AD - College of Science, School of Systems Biology, George Mason University, Manassas, VA 20110, USA. AD - College of Science, Department of Biology, George Mason University, Fairfax, VA 22030, USA. FAU - Britt, Clayton M AU - Britt CM AD - Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA. AD - Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA. FAU - Schaffer, David K AU - Schaffer DK AD - Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA. AD - Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA. FAU - Alem, Farhang AU - Alem F AUID- ORCID: 0000-0002-4288-2502 AD - Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA. FAU - Brown, Jacquelyn A AU - Brown JA AD - Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA. AD - Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA. FAU - Wikswo, John P AU - Wikswo JP AD - Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA. AD - Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA. AD - Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA. AD - Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. FAU - Narayanan, Aarthi AU - Narayanan A AD - Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA. AD - College of Science, Department of Biology, George Mason University, Fairfax, VA 22030, USA. LA - eng GR - UH3 TR002097/TR/NCATS NIH HHS/United States GR - UH3TR002097/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20221215 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 SB - IM MH - Humans MH - Animals MH - Horses MH - *Encephalitis Virus, Venezuelan Equine/physiology MH - Blood-Brain Barrier MH - *Encephalomyelitis, Venezuelan Equine/drug therapy/prevention & control MH - Endothelial Cells MH - Microphysiological Systems PMC - PMC9786295 OTO - NOTNLM OT - RTA408 OT - Venezuelan Equine Encephalitis Virus OT - alphaviruses OT - blood brain barrier OT - neurovascular unit (NVU) OT - omaveloxolone OT - organ-on-a-chip COIS- The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2022/12/27 06:00 PMCR- 2022/12/15 CRDT- 2022/12/23 02:07 PHST- 2022/11/23 00:00 [received] PHST- 2022/12/11 00:00 [revised] PHST- 2022/12/13 00:00 [accepted] PHST- 2022/12/23 02:07 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/27 06:00 [medline] PHST- 2022/12/15 00:00 [pmc-release] AID - v14122799 [pii] AID - viruses-14-02799 [pii] AID - 10.3390/v14122799 [doi] PST - epublish SO - Viruses. 2022 Dec 15;14(12):2799. doi: 10.3390/v14122799.