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

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). In this multimodal longitudinal MRI study 14 PASC participants with CI and 1...

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Bibliographic Details
Published in:	Frontiers in neurology Vol. 15; p. 1350848
Main Authors:	Chaganti, Joga, Poudel, Govinda, Cysique, Lucette Adeline, Dore, Gregory J, Kelleher, Anthony, Matthews, Gael, Darley, David, Byrne, Anthony, Jakabek, David, Zhang, Xin, Lewis, Marrissa, Jha, Nikhil, Brew, Bruce James
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 02-05-2024
Subjects:	BBB diffusion tensor imaging glutamatergic excitotoxicity MRI Neurology PASC-CI diffusion tensor imaging BBB PASC-CI MRI glutamatergic excitotoxicity
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Summary:	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). 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. 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) ( < 0.01) as well as in brain stem ( < 0.05), and higher FA and lower MD in the FWM ( < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline ( < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans). 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Wakiro Sato, National Center of Neurology and Psychiatry, Japan Edited by: Alina Gonzalez-Quevedo, Instituto de Neurología y Neurocirugía, La Habana, Cuba Sergio Gonzalez-Garcia, University of Havana, Cuba
ISSN:	1664-2295 1664-2295
DOI:	10.3389/fneur.2024.1350848