Even Without Concussion, Football Players May Show Signs of Brain Trauma

Elizabeth Millard

December 21, 2021

Even if a college football player is assessed for concussion and given the all clear, longer-term brain trauma may still be present, according to a new study in the journal iScience.

Researchers evaluated measures of metabolomic, neuroinflammatory microRNAs (miRNAs), and motor-control exercises to investigate the effects of a single season of collegiate American football on 23 players. Nine of them had experienced one to two concussions in the previous season.

Testing showed that even absent a concussion in the current season, the participants had abnormal regulation of inflammation and less coordinated movement — assessed using a virtual reality simulator that measured balance, spatial memory, and other parameters — as well as abnormalities in mitochondrial function. These markers all increased throughout the season, as more head impacts occurred.

The findings point to the possibility that significant relationships among energy-related metabolites, neuroinflammatory miRNAs, and motor control in collegiate athletes that could be applied to multiscale biology problems, the researchers noted. Fatty acids were a critical link between elevated miRNAs and motor control. Players with repetitive and cumulative head impacts showed increases in medium-chain fatty acids that could not be metabolized. Together, the observations point to brain-related mitochondrial dysfunction.

Certain neuroinflammatory miRNAs found to increase during the study period have been linked to changes in perfusion of blood in the brain, “grounding the current findings in clear neurophysiological abnormalities in brain regions that are important for motor control and spatial behavior,” the authors wrote.

Years of playing experience and a history of concussion did not appear to affect the results, the researchers noted.

Although more research is needed, particularly on a larger number of participants over a longer time frame, these findings do raise concerns about the effects of impacts overall, according to lead researcher Nicole Vike, PhD, Feinberg School of Medicine at Northwestern University, Chicago, Illinois. Not only is inflammation problematic, but the abnormal production of energy may also be harmful over time, she said.

Nicole Vike

“These abnormalities are definitely alarming given that athletes showed no signs of physical or behavioral impairment," Vike said. "Following further testing, these measures could be applicable in instances where concussion is not apparent, but suspected. They could also be incorporated into routine off-season assessments. This last point raises something else: The measures we used that are related to inflammation have been reported to be elevated even before contact practices begin.”

Given the findings, Vike and her colleagues said they believe athletes have a chronic problem, especially since they may be accruing damage over years of play, which could lead to downstream dysregulation of energy production.

"For this reason, these measures of inflammatory regulation should be considered in routine athlete assessments, regardless of concussion," she said.

Should Inflammation Be a Sideline Test?

Mounting research indicates that football can take a serious toll on the brain. A recent study found that professional football players appear to have nearly four times the risk of developing amyotrophic lateral sclerosis as men in the general population, with the risk greatest among long-term players.

Meanwhile, a study published in January 2021 found that college football players often downplayed their risk of head injuries. In one analysis, 91% of athletes underestimated their risk of injury and 63% underestimated their risk of concussion. A more conservative analysis found that 43% underestimated their risk of injury and 42% underestimated their risk of concussion.

One of the benefits of focusing on inflammation is that it can be measured through a blood test, which could be administered on the sidelines or in a locker room, said Santosh Kesari, MD, PhD, a neurologist at Providence Saint John's Health Center in Santa Monica, California. Kesari, who was not involved with the new study, said the findings highlight the danger of chronic inflammation that can result from multiple head impacts.

“One aspect of sports we don't tend to think about is inflammation, even though it ties many disorders together, and clearly trauma injury raises inflammation,” Kesari said. “When you already have a high level of inflammation and an injury brings that up even more, you'll potentially see more problems.”

At some point, an easy blood test could be implemented to pull players from games as a preventative step, he added. Doing so might mitigate permanent damage.

Although the study was limited in scope, it does help bring awareness to the concept of sub-concussive head impacts and their potentially long-term outcomes, said Ilan Danan, MD, a sports neurologist and pain management specialist at the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Kerlan-Jobe Institute in Los Angeles, California.

“Some would argue that we should be more concerned about these than concussions,” Danan said. “That's because we automatically remove someone with a concussion from play. But for someone who doesn’t get that diagnosis, they may be sent back in and have long-term damage from more head impacts.”

Greater focus on prevention strategies, such as limiting or eliminating head impact during practice, could have an effect, Danan added. Most of all, clinicians, coaches, and athletes should be aware that just because someone may not have symptoms of a concussion, they remain at risk when head impacts are part of the game.

A co-author of the study, Linda Papa, is the inventor of a patent application filed by Uniformed Services University of the Health Sciences regarding the potential utilities of selected miRNAs as diagnostic biomarkers for traumatic brain injury.

Vike, Nicole, et al. A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality. iScience. Published online December 15, 2021. https://doi.org/10.1016/j.isci.2021.103483

Elizabeth Millard is a Minnesota-based freelance writer specializing in health and sports medicine.

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