Sub-concussive hits trigger autoimmune brain damage?

Concussion - from wikipediaIn football players who take lots of hits to the head, their immune system may be attacking their brain.

That shouldn’t be possible, because a healthy blood-brain barrier keeps antibodies firmly on the body side - but new research shows that even sub-concussive hits can cause that barrier to leak. Brain proteins spill through to the body, and antibodies to those proteins can enter the brain, potentially destroying cells.

That means that the long-term brain damage seen in football players and boxers may be, essentially, an autoimmune disease.

(The study was published today in PLOS One. By the way, did you know it’s Brain Injury Awareness Month?)

Why little hits are a big deal

It took long enough to recognize concussion in sports as a serious brain injury, proably because symptoms can seem so minor. It may not be a silent killer, but it’s a silent brain-damager.

An athlete who gets a concussion may feel fine. But when her neurons stretch during the hit, and as they try to repair themselves afterward, her brain is both seriously damaged, and vulnerable to further damage if she gets a second concussion before the first is healed. (In the literature, concussion goes by the near-oxymoron “mild traumatic brain injury.”)

It used to be that loss of consciousness was the marker of a concussion. Then, it was the marker of a bad concussion. Now we know that concussions can have very subtle symptoms, detectable by computerized or app-based tests.

Now evidence has been mounting over the last decade that even smaller hits add up.

High school soccer players, in a study published last week, showed subtle changes after practice in their ability to point away from an object on a tablet-based app. I wasn’t crazy about the study because the control group hardly seemed comparable (non-athlete students) but the results are along the lines of what we’d expect to see if sub-concussions are a problem: subtle brain damage after minor hits to the head.

(Heading a soccer ball was legally ruled the cause of English player Jeff Astle’s death in 2002, although players say the ball was heavier back then, and the hits would have been pretty severe.)

When the body attacks the brain

Then comes the study published today in PLOS One. Rather than looking at cognitive deficits, they tested college football players’ blood for S100B, a protein that’s found in the blood after brain injury and, the authors say, is an accepted marker of concussion.

Wait a second - a blood test for concussion? Did I hear that right? The authors say S100B is used in Europe to rule out brain injury (no S100B, no need for a CT scan) and someday might be used as an emergency room concussion test. (That’s a good start, but an ER can’t provide concussion management nor a blanket “return to play on such-and-such date.” Just sayin.)

The bottom line on football players’ S100B: it spiked after games, but returned to baseline within 24 hours. The more head hits they’d had in the game, the higher the S100B levels. (Nobody in the study had a concussion.) This suggests that the blood-brain barrier is breached during each game, letting those proteins into the bloodstream when they should be staying in the brain.

Blood-brain barrier schematic

The blood-brain barrier. S100B comes from astrocytes, the orange guys shown here on the brain side. It shouldn’t be able to get past the blue cells into the blood … but sometimes it does.

Once in the body, the immune system builds up antibodies to S100B, legitimately thinking (if immune cells could think) that it shouldn’t be there.

The next time the player takes a hit, and the blood-brain barrier opens up again, those antibodies can cross into the brain, attacking the protein at its source. This study didn’t look at brain damage directly, but they did find that although S100B always returned to baseline, the anti-S100B antibodies increased steadily throughout the season.

What changes now?

We already knew that the blood-brain barrier is breached in traumatic brain injury, and that the breach can be both the effect and the cause of inflammation (probably both, in a vicious cycle). We know that autoantibodies are involved in other brain diseases, like MS.

Knowing that concussion and sub-concussive hits cause an immune attack on the brain - if this does turn out to be the mechanism for impairment and CTE - gives a lot of ammunition to people who are trying to limit hits in sports.

It also opens up the possibility of a way to monitor hits: rather than expensive helmet sensors, or a crude count of concussion-level injuries, players could be tested for anti-S100B antibodies once or twice a season.

Of course, the more we know about brain injury in sports, the more it makes (some of) us squeamish about playing them at all. Is there enough harm to justify banning high-risk sports? Is there a level of brain injury we can consider “safe”? Maybe not, and that’s a scary proposition for a sports fan. Or player. Or player’s mom or dad.

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