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

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

  • Viruses. 2022 Dec 15;14(12):2799. doi: 10.3390/v14122799.
Niloufar A Boghdeh 1,  Kenneth H Risner 1 2,  Michael D Barrera 1 2 3,  Clayton M Britt 4 5,  David K Schaffer 4 5,  Farhang Alem 1,  Jacquelyn A Brown 4 5,  John P Wikswo 4 5 6 7,  Aarthi Narayanan 1 3
Affiliations

Affiliations

  • 1 Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA.
  • 2 College of Science, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
  • 3 College of Science, Department of Biology, George Mason University, Fairfax, VA 22030, USA.
  • 4 Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA.
  • 5 Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA.
  • 6 Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
  • 7 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
PMID: 36560802 DOI: 10.3390/v14122799
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.

Keywords

RTA408; Venezuelan Equine Encephalitis Virus; alphaviruses; blood brain barrier; neurovascular unit (NVU); omaveloxolone; organ-on-a-chip.

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