Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection

William Schreiber-Stainthorp, Jeffrey Solomon, Ji Hyun Lee, Marcelo Castro, Swati Shah, Neysha Martinez-Orengo, Rebecca Reeder, Dragan Maric, Robin Gross, Jing Qin, Katie R. Hagen, Reed F. Johnson and Dima A. Hammoud ()
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William Schreiber-Stainthorp: Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH)
Jeffrey Solomon: Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research
Ji Hyun Lee: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Marcelo Castro: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Swati Shah: Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH)
Neysha Martinez-Orengo: Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH)
Rebecca Reeder: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Dragan Maric: Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health
Robin Gross: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jing Qin: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Katie R. Hagen: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Reed F. Johnson: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Dima A. Hammoud: Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH)

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Ebola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood–brain barrier disruption, likely related to high cytokine levels and endothelial viral infection, with extravasation of fluid, Gadolinium-based contrast material and albumin into the extracellular space. Increased glucose metabolism is also present compared to the baseline, especially in the deep gray matter and brainstem. This regional hypermetabolism corresponds with mild neuroinflammation, sporadic neuronal infection and apoptosis, as well as increased GLUT3 expression, consistent with increased neuronal metabolic demands. Neuroimaging changes are associated with markers of disease progression including viral load and cytokine/chemokine levels. Our results provide insight into the pathophysiology of CNS involvement with EBOV and may help assess vaccine/treatment efficacy in real time.

Date: 2021
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DOI: 10.1038/s41467-021-23088-x

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