Concussions sustained on the football field and in other sports have been linked to brain trauma and a disease that can cause Alzheimer's-like symptoms in athletes once their playing days are over.
A new study of college football players, however, suggests even in the absence of concussions, players may suffer long-term brain damage.
"Although the awareness of sports-related concussions is much higher, we still know very little about the long-term consequences and what happens inside the brain," the study's co-author Dr. Jeffrey J. Bazarian, associate professor of emergency medicine at the University of Rochester Medical Center in N.Y., said in a statement.
Researchers at the Cleveland Clinic and the University of Rochester collaborated on the study which looked at 67 college football players who suited up for the University of Rochester Yellowjackets, Baldwin Wallace University Yellow Jackets (of Berea Ohio) and John Carroll University Blue Streaks (in University Heights, Ohio). The researchers watched game tape of players to record the number of hits they received, and interviewed each player after the game to see if they had concussive symptoms. Players were assigned a score from zero to six based on the number of hits they endured.
Blood tests were also given to each players. Having a concussion during a game excluded players from the analysis, which made this study unique, lead researcher Dr. Damir Janigro, director of cerebrovascular research at Cleveland Clinic's Lerner Research Institute, told CBSNews.com.
Janigro explained that his team wanted to take blood tests from the players to look for a particular type of protein called S100B. S100B is used as a blood marker for traumatic brain injury (TBI) that indicates damage to the blood-brain barrier and is sometimes used to diagnose brain injuries in Europe, he said.
That barrier is a semi-permeable layer that prevents certain molecules from entering the brain from the bloodstream -- such as toxic substances from anticancer drugs -- while allowing other molecules in, such as drugs that target the brain.
Janigro added that once S100B enters the bloodstream, the immune system sees it as a foreign invader, and releases fighter molecules, or antibodies, against the protein. Those antibodies can get back through the damaged blood-brain barrier and attack brain tissue, leading to long-term damage like epilepsy and dementia.
In patients with multiple sclerosis, the immune system attacks protective sheaths around brain cells called myelin, according to the researchers.
Players in the study had their blood tested one hour before games and 25 hours after games, and also after the season and six months after the season had ended. The researchers wanted to see how these hits that weren't concussions, dubbed subconcussive episodes, affected players brains.
The researchers found varying degrees of S100B in the players: Those who had no hits and a score of zero (some special teams players) had no elevation of S100B. Those who had scores between one and six had varying degrees of elevation.
"We were surprised that even though nobody had a TBI or concussion, some hits caused SB100," said Janigro. "We were not sure what it meant."
Some players had S100B increases every time they played, which suggests one game wasn't enough to lead to damage, he said. Five players showed S100B antibodies in their blood, "interpreted as the body mounting an immune response against the protein," according to Janigro. He added that these players had the most hits to the head and the highest levels of S100B proteins on the blood tests.
MRI brain scans were given to players and showed there were subtle but measurable changes after the season was over and six months later before the start of the next season, which were consistent with risk factors for brain damage.
"What is remarkable, I believe, is that these changes were persistent -- six months after the last game," said Janigro.
He said his findings can lead to two approaches for future research. One would be the development of a blood test that can be given to players during a game to see if they've sustained damage. The other approach is to measure antibodies and brain proteins during the entire career, to see if there's a threshold when athletes should stop playing before they risk further injury.
"I think we should put more effort in looking at subconcussive episodes altogether," he said.
The study was published March 6 in PLoS One.
Last June, Dr. Ann McKee, co-director of Boston University's Center for the Study of Traumatic Encephalopathy, also toldthat more attention needs to be paid to hits that aren't' concussions.
Subconcussions cause the same traumatic injury without the symptoms and McKee estimated the average lineman endures up to 1,200 subconcussive hits over the course of a season.
McKee's center has been referred to as the NFL's "brain bank" for studies on professional football players that found evidence of the brain disease chronic traumatic encephalopathy (CTE) in autopsies of former players. The center also studies other athletes including professional hockey players, boxers, and college and high school players.
CTE in football players has been gaining attention in recent years with the high-profile suicides of former NFL starsand .
Dr. Steven Galetta, chair of neurology and co-director of the concussion center at NYU Langone Medical Center in New York City, told HealthDay that there were questions with how these subconcussive hits were defined and recorded, but added the potentially interesting findings could spur further research.
"This is a very important topic, and the more research, the better," he said. "But, right now, we're in the very early stages, and this is very preliminary."