Slow Blood-to-Brain Transport Contributes to Barrier Dysfunction in Football Players

By Will Boggs MD

June 16, 2020

NEW YORK (Reuters Health) - Slow blood-to-brain transport appears to be a major contributor to the blood-brain barrier (BBB) dysfunction resulting from repetitive mild traumatic brain injury (TBI) in American football players, according to an MRI study.

"Identifying microvascular injuries in individuals may help better understand the implications of such injuries and identify early players at risk of developing long-term damage," Dr. Alon Friedman of The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, in Beer-Sheva, Israel, told Reuters Health by email.

Dr. Friedman and colleagues recently used a modified dynamic contrast-enhanced (DCE) MRI approach to detect, localize and track subtle BBB dysfunction. In the present study, they used this method to evaluate impairments in brain microvascular function in 42 adult male amateur American football players and a control group of 27 athletes practicing noncontact sports and 26 nonathletes. They also obtained MRI scans from 51 patients with brain pathologies involving the BBB.

Permeability maps showed an increase in slow blood-to-brain transport in a subset of the football players, but not in sex- and age-matched controls.

Increased slow blood-to-brain transport was seen in white matter, midbrain peduncles, red nucleus and temporal cortex and correlated with changes in white-matter integrity.

Increased permeability persisted for months after the end of the football season, the researchers report in Brain.

BBB dysfunction was also associated with slow contrast-agent accumulation in patients with brain tumors, ischemic stroke, or hemorrhagic traumatic contusion.

Slow contrast enhancement was also apparent with focal BBB dysfunction in a rodent model of repeated mild closed-head injury and in a rodent model of vascular injury.

This slow tracer accumulation appeared to result from increased transcellular endothelial transport rather than from increased paracellular diffusion.

"Our data showing persistent leaky BBB in young, active American football players, suggest that this early pathology could serve for early diagnosis and monitoring of players at high-risk of developing delayed complications," the authors note.

"Such new diagnostic approach may serve as a monitoring tool for assessment of recovery following traumatic brain injury," Dr. Friedman said. "Finally, the proposed approach can be used in various brain and psychiatric disorders to identify subgroups of individuals with vascular pathology, better understand mechanisms of brain disorders, and hopefully such approach may not only (serve as) a diagnostic tool, but also an approach to monitor the effect of treatment."

Dr. Adnan A. Hirad of the University of Rochester Medical Center, in Rochester, New York, who recently described reductions in midbrain white matter integrity in collegiate football players, told Reuters Health by email, "We showed white matter disruption in the midbrain in a hypothesis-driven manner - now this group is showing BBB disruption in that same region. Between historical data, our paper, and this paper, this region is shaping up to be a signature region of TBI-related injury and could potentially serve as a biomarker region."]

"We need varied tools for diagnosis, treatment, and prognosis of this mechanical injury - the neurovascular-based methodology and process laid out so well here adds to that important tool kit," he said.

"Much remains unknown about short-term and long-term injury related to American football, but the scientific consensus is that it is harmful for the brains of its practitioners," Dr. Hirad concluded.

SOURCE: Brain, online May 28, 2020.