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Cited by 29Mosquito-borne diseases and controlInfectious Encephalopathies and EncephalitisBarrier Structure and Function Studies

Characterization of brain inflammation, apoptosis, hypoxia, blood-brain barrier integrity and metabolism in Venezuelan equine encephalitis virus (VEEV TC-83) exposed mice by in vivo positron emission tomography imaging

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Bocan, Thomas M., Stafford, Robert G., Brown, Jennifer L., Akuoku Frimpong, Justice, Basuli, Falguni, Hollidge, Bradley S., Zhang, Xiang, Raju, Natarajan +2 more·2019·Viruses
DOI 10.3390/v11111052PMC PMC6893841
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Abstract

Traditional pathogenesis studies of alphaviruses involves monitoring survival, viremia, and pathogen dissemination via serial necropsies; however, molecular imaging shifts this paradigm and provides a dynamic assessment of pathogen infection. Positron emission tomography (PET) with PET tracers targeted to study neuroinflammation (N,N-diethyl-2-[4-phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide, [18F]DPA-714), apoptosis (caspase-3 substrate, [18F]CP-18), hypoxia (fluormisonidazole, [18F]FMISO), blood–brain barrier (BBB) integrity ([18F]albumin), and metabolism (fluorodeoxyglucose, [18F]FDG) was performed on C3H/HeN mice infected intranasally with 7000 plaque-forming units (PFU) of Venezuelan equine encephalitis virus (VEEV) TC-83. The main findings are as follows: (1) whole-brain [18F]DPA-714 and [18F]CP-18 uptake increased three-fold demonstrating, neuroinflammation and apoptosis, respectively; (2) [18F]albumin uptake increased by 25% across the brain demonstrating an altered BBB; (3) [18F]FMISO uptake increased by 50% across the whole brain indicating hypoxic regions; (4) whole-brain [18F]FDG uptake was unaffected; (5) [18F]DPA-714 uptake in (a) cortex, thalamus, striatum, hypothalamus, and hippocampus increased through day seven and decreased by day 10 post exposure, (b) olfactory bulb increased at day three, peaked day seven, and decreased day 10, and (c) brain stem and cerebellum increased through day 10. In conclusion, intranasal exposure of C3H/HeN mice to VEEV TC-83 results in both time-dependent and regional increases in brain inflammation, apoptosis, and hypoxia, as well as modest decreases in BBB integrity; however, it has no effect on brain glucose metabolism.

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  • VEEV infects neurons and glial cells in the CNS, promoting neurodegeneration and potentially leading to permanent neurological sequelae during its lymphotropic and neurotropic phases.

    “It infects neurons and glial cells in the CNS, promoting neurodegeneration and potentially leading to permanent neurological sequelae during its lymphotropic and neurotropic phases (Bocan et al., 2019; Gleiser et al., 1962; Schoneboom et al., 2000).”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Bocan et al., 2019

    The Introduction (page not provided) describes lymphotropic and neurotropic phases of VEEV infection in mice. The Discussion (page not provided) identifies neurons as primary target cells and reports neuronal death, but describes microglial activation rather than infection of glial cells. It does not establish permanent neurological sequelae. (LLM, conf=0.88)

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Authors
Bocan, T. M., Stafford, R. G., Brown, J. L., Akuoku Frimpong, J., Basuli, F., Hollidge, B. S., Zhang, X., Raju, N., Swenson, R. E., & Smith, D. R.
Affiliations
  • United States Army Medical Research Institute of Infectious Diseases (US)
  • General Dynamics (United States) (US)
  • Foundational Sciences Directorate, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Ft. Detrick, MD 21702, USA
  • National Institutes of Health (US)
  • Naval Medical Research Command (US)
Corresponding author
Bocan, Thomas M.
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2019-11-13
Volume
11
Issue
11
Pages
1052
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v11111052
PMC
PMC6893841
OpenAlex
W2985189437
Cited by
29
References
33
Citations by year
2026: 4 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 1
FWCI
2.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
Venezuelan equine encephalitis virus, neuroinflammation, apoptosis, hypoxia, blood-brain barrier integrity, brain glucose metabolism, [18F]DPA-714, 18F-fluoromisonidazole, 18F-FDG, intranasal infection, C3H/HeN mice, olfactory bulb, brainstem
MeSH terms
Positron Emission Tomography Computed Tomography, Animals, Hypoxia, Blood-Brain Barrier, Disease Models, Animal, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Horses, Image Processing, Computer-Assisted, Biomarkers, Apoptosis, Radiopharmaceuticals, Positron-Emission Tomography, Mice

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