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Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment : Potential biomarkers and a window into pathogenesis
Chaganti, Joga Poudel, Govinda Cysique, Lucette Adeline Dore, Gregory J. Kelleher, Anthony Matthews, Gael Darley, David Byrne, Anthony Jakabek, David Zhang, Xin
Chaganti, Joga
Poudel, Govinda
Cysique, Lucette Adeline
Dore, Gregory J.
Kelleher, Anthony
Matthews, Gael
Darley, David
Byrne, Anthony
Jakabek, David
Zhang, Xin
Abstract
Objective: To investigate the association between blood–brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC).
Methods: In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores.
Results: At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans).
Interpretation: PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.
Keywords
Date
2024
Type
Journal article
Journal
Frontiers in Neurology
Book
Volume
15
Issue
Page Range
1-9
Article Number
Article 1350848
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open
Notes
© 2024 Chaganti, Poudel, Cysique, Dore, Kelleher, Matthews, Darley, Byrne, Jakabek, Zhang, Lewis, Jha and Brew. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) 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.