OT: study suggests college football players at risk of brain damage even without concussions

Submitted by dnak438 on March 6th, 2013 at 6:23 PM

An academic study was published today suggesting that sub-concussive events can cause brain damage in non-concussed football players. I'm not qualified to judge the scientific merits of the study, but it looks like bad news for football players. I was hoping someone in the MGoBlog community would be qualified to assess how serious and conclusive the study is.

Business week reports as follows (LINK):


Researchers at the Cleveland Clinic used blood tests, brain scans, and cognitive and other tests to assess brain trauma in 67 college football players over the course of the 2011 season. Although none of the players experienced concussions, blood tests showed that the 40 players who absorbed the hardest hits had elevated levels of an antibody linked to brain damage. These players then underwent brain scans at the University of Rochester Medical Center. When the scans were analyzed in a double-blind process, researchers found abnormalities that were predicted by the presence of the antibody.

“This positive correlation could be an early indicator of a pathological process that, with time, could perturb players’ brain health,” says Nicola Marchi, a professor of molecular medicine at the Cleveland Clinic Lerner College of Medicine, who co-authored the study with Lerner colleague Damir Janigro and Rochester’s Jeffrey Bazarian. “All football players have repeated subconcussive hits—throughout the game, the season, and their careers,” he says, but without external symptoms of injury, the hits were hard to measure. The blood tests appear to offer an early warning system.

The academic article's abstract (LINK):

The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.



March 6th, 2013 at 6:35 PM ^

plos one is a relatively low journal...meant to provide open access to its contents and a relatively favorable review process for the authors. Good and bad articles can be found there....as to the work, I am not qualified to address the content of the article itself, however.


March 6th, 2013 at 6:45 PM ^

The journal strives for a different audience.  As was correctly pointed out, you do have varying levels of quality on the journal.  The allure of open access and little politics attracted me to publish there before.  In my case, there were multiple reviewers that critiqued my work and made reasonable comments, though admittedly, it is not nearly as stringent as a 'traditional' journal.

Wisconsin Wolverine

March 6th, 2013 at 6:55 PM ^

Easy ... PLoS ONE was designed as an open access journal which evaluates submissions on quality of work alone, not the "hotness" of the topic.  That's why it's different from journals such as Nature or Science, which have high impact factors.  The trade-off is that these journals can be almost tabloid in nature - the kind of articles that get published here are cutting edge, but unreplicated.  A decent proportion of these high impact studies wash out as nothing of substance - just something that garners a lot of attention at first blush.

Additionally, PLoS has other "versions" of itself - such as PLoS Genetics & PLoS Biology.  PLoS Biology is actually a very prestigious journal with a high impact factor - but ironically, they are obligated to not advertise that fact based on their founding philosophy that impact factor is not the alpha & omega of publication.

I should also admit that I'm a big proponent of open access scientific formats, & I think it's particularly favorable for large scale studies that use a high volume of data because there are no length restrictions or limitations on how the data can be shared with the scientific community.


My two cents.


March 6th, 2013 at 8:07 PM ^

I am aware of Plos Genetics and Biology. They are quite different from Plos One. The review process is much more stringent...a critique level at or slightly below PNAS. Plos Biology is becoming an elite general. Both have strenous review processes, unlike Plos One.

As for open access, I love the concept and hope to submit to Plos Genetics soon. The only issue is I believe the amount needed to be provided by the submitting lab to cover the costs of the open access forum.


March 7th, 2013 at 1:46 AM ^


The trade-off is that these journals can be almost tabloid in nature - the kind of articles that get published here are cutting edge, but unreplicated.  A decent proportion of these high impact studies wash out as nothing of substance - just something that garners a lot of attention at first blush.


I think a strong argument can be made that Nature and Science are very much full of sensational but non-replicable findings. Admittedly, how reputable you think they are depends a lot on what field you're in (Nature, Science, and PLoS One are cross-disciplinary; most scientific journals are much more focused). In my field, I don't believe anything published in Nature until I see it published somewhere else, by someone else, at a later date. So to me, the difference between them is as much about how you feel about the open access model as it is about impact factors. But this line of conversation may rapidly approach the no politics limit, so I'll stop here.


March 7th, 2013 at 12:05 PM ^

It's a matter of "how much damage can you sustain before it alters your lifestyle."  Every time we drink alcohol, we are killing off a few brain cells, but many of us make the choice to do it anyway.  Nobody thinks they are going to become an alcoholic or destroy enough brain cells to decrease quality of life when they are having a few beers.  It's the same line of thought with "harmless" hits on a football field, but you can damage a lot more brain cells at once.

Right now, football is rewarding "big hits."  They need to figure out a way to lessen impacts without fundamentally changing the way the game is played.  Sadly, in the ultra-macho world of professional football, there will be resistance to anything that is done to lessen hitting.

It's probably going to get worse before it gets better.  It would be nice if science could figure out a way to produce and harvest stem cells in a way that doesn't cause controversy.  It would be great if the medical/science world figured out a way to replace damaged brain and spinal cells.  

At any rate, one of two things is going to happen.  Either football is going to undergo some huge changes, or science is going to figure out how to mitigate brain damage.


March 7th, 2013 at 1:02 PM ^

Just clarifying that my comment about "not believing anything in Nature until I see it somewhere else too" was directed at a discussion of the relative merits of scientific journals, not toward the actual topic at hand. I agree, it does seem that the evidence is indeed mounting that cumulative trauma to brain tissue, even sub-concussion level trauma, leads to bad news down the road.

I guess I should also clarify that when scientists talk about what is and is not believable or credible in scientific journals, they tend to approach the conversation from a different perspective than laymen discussing believability of, say, a news report. Scientific skepticism is a nuanced thing, which usually amounts to "there probably is something to this, but being a cautious scientist, I'll wait for more research to fill in the gaps in the story rather than declaring 'this study proves that x is true." This isn't at all the same kind of skepticism as "well, they're just plain wrong about this." So, for example, when I state that I "don't believe anything in Nature until I see it elsewhere," I don't actually mean I think that the authors are fudging data or lying about their findings. The high impact factors for Nature and Science are because the work reported there is in some sense the "most interesting" work being done right now, or "most cutting edge." It's not, however, the "most correct" or "most rigorous." It's exactly as rigorous as all the rest of science -- which is to say, pretty damn rigorous, but limited by the fundamental problem that real life is complicated and not always easily condensed into "A causes B with 100% certainty" types of statements. People working in science generally get pretty comfortable with, even take for granted that, there are very few situations in real life where you can say "A causes B, for certain." I suspect most non-scientists live in a more certain world, and as a result it's easy for there to be miscommunication between scientists and non-scientists about "how true" a scientific finding is. And the more politicized the topic, the more problematic this miscommunication becomes. Since few of the people who watch football, and probably none of the people involved in running the NFL, have any training in scientific thinking, there's going to be a lot of "debate" about scientific findings regarding concussions and brain damage that sounds like scientific debate, but is really non-scientists misunderstanding what scientists have said and arguing with each other in a way that's ultimately damaging to turning actual research findings into productive changes in football rules. (The worst case scenario here looks like the "scientific debate" about climate change, where most of the conversation takes place between non-scientists who anyway aren't interested in 'debate' in the proper sense.) Brace yourselves: much of what you'll hear in the next few years about the "scientific discussion about brain damage in football" will be neither particularly scientific, nor particularly useful in creating sensible changes to the rules of football (should that turn out to be necessary). That doesn't mean there won't be good science on this matter; it just means most of the people expressing opinions don't actually know what they're talking about. Which I guess makes this like every other publicly discussed topic!


March 6th, 2013 at 6:33 PM ^

Purdue researchers published a similar study in high schoolers prior to this one. Most of the brain damage could actually be caused by accumulation of sub concussive blows rather than concussions.

Willis Ward

March 6th, 2013 at 6:55 PM ^

and they found that the little collision, even in days without full pads, cumulatively did serious damage.

i'm not a doctor (and i sucked at all sciences in school) but human understanding of the brain is very limited.  doctor's don't even really understand what happens to a brain when it is concussed (other than the fact that the brain is bruised and the obvious symptoms felt by and observed of the individual).  i think these studies do the best they can given our collective lack of understanding.

Happy Gilmore

March 6th, 2013 at 7:19 PM ^

As a medical student currently about neuropathology, I can tell you that a concussion is actually defined by having transient symptoms with NO (known) abnormalities histologically ("under the microscope"). 

This is in contrast to a contusion (a more severe head injury, like getting hit with a baseball bat for example) that leads to focal areas of death of brain tissue. 

A general way to think of the brain is that around the outsides (closest to the skull, called "gray matter") are the neuron cell bodies, and these send long projections down towards the middle of the brain (called "axons" - and note that bundles of axons are what makes up nerves) and eventually out the spinal cord. A contusion is damage to these cell bodies leading to cell death that is able to be demonstrated. 

One current hypothesis is that the transient symptoms of a concussion are due to diffuse damage to the "axons" rather than injury to the cell bodies. It is documented that "shaking baby syndrome" that most people know about causes damage like this leading to dysfunction, and there is some evidence (according to my professors but not that I have read directly) suggesting that concussions may be a form of similar damage.

Regardless of the exact mechanism, I think that anyone who says that repeated head trauma (even sub-clinical, as is used in this study) does NOT, at the very least, increase the possibility of long term damage is very wrong. HOWEVER, I am not also not convinced that repeated sub-clinical trauma leads to the severity of mental illness that is being propagated in the media. 


March 6th, 2013 at 6:39 PM ^

I'm not saying it isn't conceivable. I'm not even saying it isn't probable. But this type of a situation is ripe for cum hoc non propter hoc fallacies. My favorite clinical example of that relates the tale of hormone replacement therapy (HRT) from the last 15 years. HRT was designed for postmenopausal women [...] to help balance them out. Over the last 15 years it became celebrated for a short while and then fell into disuse (because it correlates with stroke and breast/endometrial cancer risk across all demographics).

The logical fallacy part plays into why it became celebrated in the first place: There was one seminal study suggesting HRT caused a decrease in coronary artery disease (CAD). However, the study failed to consider alternative possibilities. For instance, it turns out all of the HRT-taking women in the study were of higher socioeconomic status (SES) and had, on average, the better diets and activity regimens that the higher SESs have relative to the lower SESs. Turns out HRT actually has no effect on coronary artery disease. The scientists spoke too soon--believing that just because HRT use correlated with less CAD in their study that it was causing that effect.


March 6th, 2013 at 6:47 PM ^

Admitting that science can never possess (but only assymptotically approach) objective truth, it turns out that it is nigh impossible to *prove* a cause-and-effect delineation and still very difficult to delineate one that is even persuasive. Having said that, while typing from an academic tower (I'm a recently graduated physician scientist), I've skated over the point and risk seeming heartless. I'm not hostilely doubting the relationship between collisions and brain damage. It makes plenty sense to me. But that isn't enough to satisfy the burden of proof. It's only enough to make us legitimately wonder and worry and legislate safety precautions knowing, even if we are wrong, we are treading thoughtfully.

These two posts were just about being honest that the thin gray line does exist. That a study like this, even if enough to persuade us to action, isn't itself proof of the theory.


March 6th, 2013 at 6:45 PM ^

As a member of the scientific community I fully understand the need for scientific evidence before drawing any conclusions. But the normal person side of me says "duh, banging your head against things over many years is going to result in things not working correctly." Regardless, I really hope people don't run with this and try and ban football because even everyday play can result in brain damage.

snarling wolverine

March 6th, 2013 at 7:35 PM ^

The other thing we should keep in mind is that only a small percentage of ex-football players display CTE symptoms.  They are more likely than the general population to suffer from CTE, certainly, but of all the long-term health issues they are at risk for, this isn't the highest on the list by any means.  Heart problems seem to be a much larger factor (a disturbingly large number of ex-NFL players die in middle age of heart disease), but it's not as trendy a subject in the news.

Most of the guys in this study still (presumably) were able to balance a full college courseload and learn a thick college football playbook, which requires some pretty good brain functioning to pull off.







March 6th, 2013 at 6:51 PM ^

This study is stupid.  I'm at danger of brain damage right now and I'm sitting in class taking notes.  Everybody is at risk of brain damage, it can't always be traced back to playing football.


March 6th, 2013 at 6:55 PM ^

As someone who was a walk-on at D1 school who never got any significant playing time, at 47 I am genuinely concerned about any potential damage I may have caused.

I probably had a few concussions in my 9 years of tackle football, and as I approach 50, my brain is not what it use to be. I am making more mental mistakes at work, forgetting things more often, and having moments that cause me to worry. Every day, something occurs that makes me wonder if the daily trauma of contact football is causing me to experience these things.

I've never admitted any of this before, but as time goes by, I can't ignore the possibility.

Willis Ward

March 6th, 2013 at 7:06 PM ^

I had dinner with a friend who is still in the league (been playing for 8 years now) a few weeks ago and he said he is convinced he is going to have trouble with his brain as he goes on.  He also said this is the belief of most of the league.  On the one hand, it makes me feel a little bit better that players today have a good grasp on the risks (as good of a grasp as anyone can) and then can make an educated decision about continuing to play.  On the other hand, it makes me sick everytime I hear a commentator or anyone else suggest these studies don't ring true.  Playing football puts your brain at significant risk of severe damage.  I only played 4 years in highschool, but clearly the longer you play and the more collisions (and greater f=ma) you suffer the more at risk you are.  I truly hope you are ok.  I really wish arm chair qbs would stop acting like tobacco executives.


March 7th, 2013 at 5:49 AM ^

stuff you are talking about.   maybe you should get some testing done?   i am a few years older than you, played until i was 42, but don't (at this point) think i did damage, or at least damage that has manifested itself in any way.  perhaps greater risk for some of the other things we are reading about with the pros that are having issues, but i hope not. 


March 6th, 2013 at 7:09 PM ^

but just reading the study title makes me wonder about the future of football. I'm starting to believe that we're going to find it has lasting impact on just about anyone who plays the game, and once that happens, I'm not sure where the sport goes. Two hand touch?


March 6th, 2013 at 7:16 PM ^

There are lots of examples even now of it having a lasting impact.  And like you said, I think we will start to see more examples from this generation of players who are bigger and faster.

Bill Simmons had Don Van Natta Jr. on his podcast.  He was the author of this investigative report.


They talk extensively about concussions/player safety and how it relates to the NFL/Roger Goodell.


March 6th, 2013 at 7:55 PM ^

There's too much money in football for things to change drastically soon. There will probably be a reduction in the amount of youth players, but probably not enough to make a real dent. 

I love watching football, but am glad my parents put me in hockey and will do the same for my kids (being 5'9" and white has something to do with that too haha)


March 6th, 2013 at 7:57 PM ^

Really? Lets wrap heads around the fact that football is a dangerous sport, if you ain't wanna get hurt, don't buckle up a chin strap.

I played, I sustained concussions, saw stars. I get dizzy now and then, but shit, my grades weren't effected too much to not get into Michigan.

The problem with football is not the concussions, it's the folks who don't understand the consequences taken when stepping on the field.

Would you willingly drive a car with squishy brakes? Kind of like that.

Where's the drinking thread?

Lost in Champaign

March 6th, 2013 at 8:06 PM ^

As many others have stated, there is now a substantial amount of evidence to back up the fairly intuitive idea that repeated head trauma can have a long-term negative impact. Football players offer a large sample size for these recent headlining studies. My question is when will there be more of a focus on the other sports that involve any kind of contact. Even if you forget about things like boxing and martial arts, other sports like hockey and lacrosse probably have similar long-term effects. Hell, even soccer players are taught to use their heads to move the ball around regularly. 

In the end (for better or worse), I don't actually see many changes into how any of these sports are played. There is already more of a focus on developing safer helmet and padding technology, and I expect that to continue.


March 6th, 2013 at 9:30 PM ^

I think everyone who chooses to play sports should be wrapped in bubble wrap. Of course, this would only prompt studies into the effects of athletes being wrapped in bubble wrap...


March 6th, 2013 at 10:56 PM ^

I'm not going to comment on the reaching implications, but seriously, being able to read the whole paper FO FREE is giving me a wicked halfer.


March 7th, 2013 at 11:47 AM ^

The researchers tested a lot of players but from only three teams. To me that raises some red flags regarding the validity of the study. The three teams could be teams that don't have the attention to injury that many others have. If 67 players is the number then it should have been far more teams, like 10 or more.


March 7th, 2013 at 1:13 PM ^

Wasn't it that Section 1 guy who was ranting about how only pro football put the brains of players at serious risk with absolutely no evidence of this and in denial of a lot of other studies on college and high school ball?

Yeah. Probably wrong about that.