Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players.

Autor:	Veksler R; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Vazana U; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Serlin Y; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.; Neurology Residency Training Program, McGill University, Montreal, QC, Canada., Prager O; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Ofer J; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Shemen N; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Fisher AM; Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA., Minaeva O; Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA., Hua N; Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA., Saar-Ashkenazy R; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.; Department of Psychology and the School of Social-work, Ashkelon Academic College, Israel., Benou I; Department of Electrical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Riklin-Raviv T; Department of Electrical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Parker E; Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada., Mumby G; Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada., Kamintsky L; Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada., Beyea S; Biomedical Translational Imaging Centre (BIOTIC), IWK Health Centre and QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada., Bowen CV; Biomedical Translational Imaging Centre (BIOTIC), IWK Health Centre and QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada., Shelef I; Department of Medical Imaging, Soroka University Medical Center, Beer-Sheva, Israel., O'Keeffe E; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Campbell M; Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Kaufer D; Department of Integrative Biology and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA., Goldstein LE; Molecular Aging and Development Laboratory, Boston University School of Medicine, College of Engineering, Alzheimer's Disease and CTE Center, and Photonics Center, Boston University, Boston, MA, USA., Friedman A; Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.; Department of Medical Neuroscience, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2020 Jun 01; Vol. 143 (6), pp. 1826-1842.
DOI:	10.1093/brain/awaa140
Abstrakt:	Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood-brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies. (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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