Australian Study Finds That Those With Post COVID Cognitive Issues Are Likely To Suffer From Blood Brain Barrier Disruption And Glutamatergic Excitotoxicity!
Nikhil Prasad Fact checked by:Thailand Medical News Team May 04, 2024 6 months, 2 weeks, 4 days, 5 hours, 9 minutes ago
COVID-19 News: Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID, has raised significant concerns due to its diverse and persistent symptoms. Among these symptoms, cognitive impairment (CI) has emerged as a prominent issue affecting individuals even after recovering from the acute phase of COVID-19. However, the exact mechanisms underlying PASC CI remain elusive, prompting researchers to delve deeper into the neurological aspects of this condition. In a groundbreaking study conducted across multiple institutions in Australia and the United States, a team of researchers aimed to unravel the association between blood-brain barrier (BBB) disruption, brain metabolites, white matter microstructural integrity, and cognitive impairment in individuals with PASC. This
COVID-19 News report provides an in-depth analysis of their findings, methodologies, and implications for future research and clinical practice.
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Individuals With Post COVID Cognitive Issues Are Likely To Suffer From Blood Brain Barrier Disruption And Glutamatergic Excitotoxicity. Diffusion tensor data with FA and MD on a shaded surface display and statistical maps between subjects and controls. DTI-based changes in fractional anisotropy (FA) and mean diffusivity (MD) values in patients compared to controls. (A) TBSS analysis showed significant (p < 0.05, cluster corrected) increase (red) in FA values and decrease (blue) in MD values. The color bar represents corresponding t-values. (B,C) Box plot of FA and MD values from an example FWM area (as highlighted on the brain image) showing the difference.
The Study: Methodologies and Objectives
The collaborative effort involved researchers from Thomas Jefferson University in Philadelphia, USA, Australian Catholic University in Melbourne, University of New South Wales, St Vincent’s Hospital, Royal Prince Alfred Hospital, The Canberra Hospital, and University of Notre Dame in Sydney, Australia. Their objective was clear: to investigate the intricate connections between BBB permeability, brain metabolites, white matter microstructure, and cognitive impairment in individuals experiencing post-acute sequelae of SARS-CoV-2 infection.
Using a multimodal longitudinal MRI approach, the study enrolled 14 PASC participants with CI and 10 healthy controls. The assessments were conducted at 3 months post-acute infection, with a subset of PASC participants undergoing further evaluations at 12 months. Various MRI techniques, including Dynamic contrast-enhanced (DCE) perfusion imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy, were utilized to gather comprehensive data on BBB integrity, neurochemical profiles, and white matter structural changes. Neurological assessments and cognitive screenings were also part of the evaluation process.
Findings: Unraveling the Neurological Puzzle<
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The study’s findings shed light on several key aspects:
-Blood Brain Permeability (K-trans) Changes: Participants with PASC CI exhibited significantly higher K-Trans values in the frontal white matter (FWM) and brainstem compared to healthy controls at baseline. However, there were no significant changes in K-Trans values over time within the PASC CI group.
-Brain Metabolites Alterations: PASC CI participants displayed lower GLX values and higher Myo-inositol levels in the FWM, indicating alterations in brain metabolites associated with neurotoxicity. While GLX values normalized over 12 months, Myo-inositol levels remained elevated.
-White Matter Microstructure: Analysis of DTI data revealed increased fractional anisotropy (FA) and decreased mean diffusivity (MD) in various white matter regions among PASC CI participants compared to controls, indicating changes in microstructural integrity.
-Correlation with Neurocognitive Scores: Correlational analyses between imaging metrics and cognitive scores showed no significant correlation between K-Trans and cognitive performance. However, there were associations between K-Trans and FA, as well as brainstem K-Trans and Glx levels.
Interpreting the Results: Implications for Pathogenesis and Clinical Practice
The study’s comprehensive approach unraveled potential pathways contributing to cognitive impairment in PASC:
-Blood Brain Barrier Impairment: The increased K-Trans values indicated BBB disruption in PASC CI participants, aligning with previous research highlighting the role of BBB integrity in neurological disorders.
-Neurochemical Changes: Alterations in GLX and Myo-inositol levels suggested excitotoxic neuronal injury, possibly mediated by BBB impairment. These neurochemical changes are often associated with neuroinflammation and neuronal damage.
-White Matter Integrity: The observed changes in FA and MD underscored disturbances in white matter microstructure, implicating axonal degeneration and inflammation as potential contributors to cognitive impairment.
Implications for Future Research and Clinical Management
While the study provides valuable insights, several limitations warrant further investigation:
-Sample Size and Generalizability: The small sample size limits the generalizability of findings. Future studies with larger cohorts are essential to validate these results across diverse populations.
-Longitudinal Control Data: Lack of longitudinal control data at 12 months hinders direct comparisons and comprehensive understanding of brain alterations over time.
-Neuropsychological Correlations: Limited neuropsychological assessments and mild cognitive impairment range underscore the need for robust cognitive evaluations in future studies.
Despite these limitations, the study sets a solid foundation for future research endeavors. Advanced MRI techniques addressing BBB disruption, white matter integrity, and neurochemical changes hold promise as potential biomarkers for PASC CI diagnosis, treatment timing, and therapeutic response assessment.
Conclusion
In conclusion, the Australian study illuminates the complex interplay between BBB disruption, neurochemical alterations, white matter integrity, and cognitive impairment in PASC. By unraveling these neurobiological mechanisms, researchers and clinicians are poised to develop targeted interventions and enhance clinical management for individuals grappling with post-COVID cognitive issues. As our understanding of long COVID evolves, interdisciplinary collaborations and innovative research methodologies will play a pivotal role in addressing this multifaceted health challenge.
The study findings were published in the peer reviewed journal: Frontiers in Neurology.
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1350848/full
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