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REVIEW article

Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1514940

Neurological Manifestations of Encephalitic Alphaviruses, Traumatic Brain Injuries, and Organophosphorus nerve agent exposure

Provisionally accepted
Morgen VanderGiessen Morgen VanderGiessen 1,2Caroline de Jager Caroline de Jager 1Julia Leighton Julia Leighton 3Hehuang Xie Hehuang Xie 1Michelle Theus Michelle Theus 1Erik Johnson Erik Johnson 3Kylene Kehn-Hall Kylene Kehn-Hall 1,2*
  • 1 Department of Biomedical Sciences and Pathobiology, Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, United States
  • 2 Center for Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States
  • 3 Department of Neuroscience, The United States Army Medical Research Institute of Chemical Defense, Aberdeen, Maryland, United States

The final, formatted version of the article will be published soon.

    Encephalitic alphaviruses (EEVs), Traumatic Brain Injuries (TBI), and organophosphorus nerve agents (NAs) are three diverse biological, physical, and chemical injuries that can lead to long-term neurological deficits in humans. EEVs include Venezuelan, eastern, and western equine encephalitis viruses. This review describes the current understanding of neurological pathology during these three conditions, provides a comparative review of case studies vs. animal models, and summarizes current therapeutics. While epidemiological data on clinical and pathological manifestations of these conditions are known in humans, much of our current mechanistic understanding relies upon animal models. Here we review the animal models findings for EEVs, TBIs, and NAs and compare these with what is known from human case studies. Additionally, research on NA and EEVs is limited due to their classification as high-risk pathogens (BSL-3) and/or select agents; therefore, we leverage commonalities with TBI to develop a further understanding of the mechanisms of neurological damage. Furthermore, we discuss overlapping neurological damage mechanisms between TBI, NA, and EEVs that highlight novel medical countermeasure opportunities. We describe current treatment methods for reducing neurological damage induced by individual conditions and general neuroprotective treatment options. Finally, we discuss perspectives on the future of neuroprotective drug development against long-term neurological sequelae of EEVs, TBIs, and NAs.

    Keywords: Venezuelan equine encephalitis virus, eastern equine encephalitis virus, Western equine encephalitis virus, Neuroinflammation, Traumatic Brain Injury, organophosphorus nerve agent, Neurological sequelae

    Received: 21 Oct 2024; Accepted: 20 Nov 2024.

    Copyright: © 2024 VanderGiessen, de Jager, Leighton, Xie, Theus, Johnson and Kehn-Hall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kylene Kehn-Hall, Department of Biomedical Sciences and Pathobiology, Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, 24061, Virginia, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.