Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players
| Autor: | Alon Friedman, Lee E. Goldstein, Rotem Saar-Ashkenazy, Ning Hua, Steven D. Beyea, Nofar Shemen, Chris V. Bowen, Ellen Parker, Ilan Shelef, Ofer Prager, Griffin Mumby, Matthew Campbell, Jonathan Ofer, Olga Minaeva, Andrew M. Fisher, Lyna Kamintsky, Tammy Riklin-Raviv, Daniela Kaufer, Ronel Veksler, Itay Benou, Yonatan Serlin, Eoin O'Keeffe, Udi Vazana |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology Poison control blood–brain barrier Medical and Health Sciences Brain Ischemia 0302 clinical medicine Craniocerebral Trauma Temporal cortex Brain Magnetic Resonance Imaging White Matter repetitive mild traumatic brain injury Stroke Diffusion Tensor Imaging medicine.anatomical_structure Tauopathies Blood-Brain Barrier Adult medicine.medical_specialty Adolescent Traumatic brain injury Football transcellular transport tau Proteins Neuropathology Blood–brain barrier Chronic Traumatic Encephalopathy White matter 03 medical and health sciences medicine Animals Humans Brain Concussion American football Neurology & Neurosurgery business.industry Psychology and Cognitive Sciences Original Articles blood-brain barrier medicine.disease United States Rats Chronic traumatic encephalopathy 030104 developmental biology Athletes Microvessels dynamic contrast-enhanced magnetic resonance imaging Sprague-Dawley Neurology (clinical) business 030217 neurology & neurosurgery Diffusion MRI |
| Zdroj: | Brain Brain : a journal of neurology, vol 143, iss 6 |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awaa140 |
| Popis: | See Ware et al. (doi:10.1093/brain/awaa166) for a scientific commentary on this article. Using a modified MRI-based method that can detect subtle, region-specific blood-brain barrier dysfunction, Veksler et al. reveal slow blood-to-brain transport in a subset of amateur American football players. MRI may allow early detection of microvascular pathology in patients at risk for chronic traumatic encephalopathy. 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. |
| Databáze: | OpenAIRE |
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