Boxing's Most Important Issue: A Look Into Traumatic Brain Injury Research
Sean Mills returns to Bad Left Hook today to look at boxing's most troubling problem, and the research done by a Notre Dame doctor.
The greatest single threat to the sport of boxing is a moving target. For some people, steroid allegations have made Olympic style drug testing the number one concern. Others think it's the need for a new commission, one that could prevent questionable decisions and championship gerrymandering. Jim Lampley, a color commentator for HBO once called the floor decals used as advertisement in the ring itself as the biggest problem in boxing, because they cause boxers to slip an injure themselves. However, all of these choices pale in comparison to this the most basic element of the game: the lasting mental health of boxers.
If you are a sports fan, chances are you watch multiple sports. So, you may have already seen the television commercials for a research program headed by Dr. Mayland Chang at the University of Notre Dame. During this season's Notre Dame versus USC game (which Notre Dame could have won if it didn't fumble in the red zone), we learned that Dr. Chang is the recipient of an NFL grant, which allows her to continue studying ways to prevent damage from traumatic brain injuries.
At Notre Dame where Dr. Chang performs her research, alumnus-boxer Mike Lee recently brought professional boxing to campus. And while the National Football League provides funding because of injuries from hard tackling, the true beneficiary might really prove to be boxers. There are many pathological issues that plague boxing; this is to be expected perhaps from the nature of the game.
Understandably, Chang's work is complex and one struggles to fully understand the technical language written in medical journals. However, from her interviews and public statements an exciting picture develops:
The idea is that after a traumatic brain injury, enzymes in the fluid of the brain eventually begin to kill brain tissue. Chang's research has isolated an inhibitor, which may prevent the "destined brain damage." The hope is to provide a treatment for athletes, which will provide quick-response intravenous solution to the body, essentially saving part of the patient's brain.
It's natural to wonder if such a treatment would be applied to the concussion-prone field of boxing. Would this procedure be administered to boxers immediately after a fight? Could this procedure be administered after every fight?
I contacted Dr.Mayland Chang, at the University of Notre Dame to find the answers to these questions and have her clarify in her own words:
"Following a traumatic brain injury (TBI), there is a primary injury caused by the blow, followed by a cascade of biochemical events that leads to secondary injuries hours to days after the initial injury. Gelatinase B (also referred to as matrix metalloproteinase-9, MMP-9) is at the top of the cascade and is responsible for the events leading to blood-brain barrier damage, death of brain cells, swelling, inflammation, hemorrhage, cognitive and emotional disabilities.
The idea is to protect the brain from the cascade of events that lead to further/permanent damage by inhibiting MMP-9. We hope to be able to help patients who suffer a TBI in the early stages (hours to days). We envision that such a treatment will be given to athletes, including boxers, who suffer a TBI soon after the injury. This therapy is not recommended to be given as a prophylactic since MMP-9 is not present in the uninjured brain.
So while the compound may not be toxic, it will not provide a benefit if the therapy is administered without a TBI. While we have indication that the compound is not toxic, we have not yet conducted toxicology studies in animals at high doses, which are required before advancing the compound to clinical trials in humans."
While Dr. Chang's deserves attention from the public, one wonders what the medical experts familiar with the sport of boxing are making of her progress. I contacted the Association of Boxing Commissions to find out. Dr. Sherry Wulkan, the Chair of the ABC Medical Committee had this to say:
"The work of these researchers should be commended both for the thoroughness in its execution and, because of the long term implications it may have on the treatment and outcome of stroke patients, patients with TBI, spinal injuries, aneurysms and atherosclerosis. Their work may also theoretically impact cancer therapy in that MMP-9 inhibitors are believed to alter the natural history of tumor invasion and metastasis. While clearly exciting, further research still needs to be done regarding the potential toxicities of these newly derived compounds before clinical trials will be approved by the FDA."
So while boxers wait for this treatment to be fully tested, the possible development of a partial antidote to traumatic brain injury cell death is encouraging news for everyone.
According to report by the U. S. Department of Health and Human Services, 1.7 million concussions are reported per year. Most of these occur from falls, next by automobile accidents, then by blows, and finally causes unknown. Unfortunately, it's not possible to catch all cases.
A troubling quote brings to mind the victims among retired boxers that are casually called "punchy."
"TBI is frequently referred to as the 'silent epidemic' because the complications from TBI, such as changes affecting thinking, sensation, language, or emotions, may not be readily apparent. In addition, awareness about TBI among the general public is limited."
For more information on traumatic brain injury you can check the CDC website here.
For more information on Dr. Chang's research you can check her website here.
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Outstanding work.
Let’s hope there is solid long-term footing for the research. Fingers crossed.
Wear something sexy to my funeral.
Promising research, but the MMP-9 inhibitor has only been performed on animals (low dosages), so how it would perform (including toxicity) on humans is an interesting question.
You have to administer this inhibitor rather quickly. Since TBI is a "silent epidemic" , and changes are not "readily apparent" ,recruiting acutely affected TBI subjects may be a challenge.
Great writeup man
Interesting stuff.
"Boxing is like dealing with a ho"
-Bernard Hopkins
Nice article.
Did you come across any reference to the types of improvement that the treatment could translate into? In other words, it sounds like this has the potential to help stop the cascade of injuries after the initial trauma. What part of the brain injury pie, so to speak, are caused in this subsequent phase (vs. the damage caused by initial trauma)? Not even sure that that’s answerable – just curious. And any progress that may help save a life is worth pursuing. Interesting stuff.
You hit the nail on the head, it is a tough question to answer.
I started writing an article about all the different types of brain damage ringside doctors are supposed to “look out for” before I shifted my focus. I am by no means an expert, but the snap answer to your question is that it varies greatly from each specific fight as to what kinds of damage would possibly be preventable.
From my understanding,once the brain fluid is scrambled by a injury much of the health impact is not from the tearing action or impact to the brain instantly but rather the resulting “poisoning” of the chemical imbalance.
What we do know is that if there was a good reason to believe that a concussion occurred, if this research pans out, the treatment would be given immediately, which is the only way it could help.
I am thinking of going back to an in depth break down of the brain traumas specific to boxing, but I probably want to find an experienced ringside physician and pick his brain first.
More advanced TBI pharmaceutical
Hi Sean,
Your excellent article came up on my google alert for TBI.
I just wrote an article for a pharmaceutical magazine (“Cyclosporine: TBI’s Miracle Drug”) that explains what occurs during the secondary stage of TBI and exactly how the chemical imbalances cause brain cell death. This may be of interest. It turns out that the imbalances cause the brain cell’s mitochondria to pop like balloons and collapse. When enough mitochondria die the brain cell dies. FYI, the mitchondria are the power plants that power all cells in the body – including brain cells and muscles. When athletes train super hard, they are actually training their muscle mitochondria to be more powerful.
As you mention, TBIs ripen and worsen during the secondary stage in the period after the initial injury for a few days. This is the time where doctors say, “Now we just wait and see.” During this time the mitochondria cellular power producers cell are under attack by the chemical imbalances and are collapsing by the thousands inside each brain cell with the result that millions of additional brain cells can die due to lack of energy. Protecting the mitochondrial cellular power producers has emerged over the last decade as a key strategy in limiting brain cell death and reducing the eventual disability of TBI.
My article – which is referenced to peer-reviewed studies but is not too scientific – explains what happens in this secondary stage. It explains that cyclosporine has outstanding promise as a TBI medicine because it has been proven to protect the brain’s mitochondria from those cascading chemical imbalances. This protection allows those millions of brain cells to keep being powered while healing occurs. (Disclosure: my client – NeuroVive Pharma www.neurovive.com – is developing cyclosporine as a TBI medicine called NeuroSTAT. The magazine editor requested the company write an objective scientific article backed up by reference to published studies explaining cyclosporine’s impact on TBI.)
As for MMP-9 and other potential avenues of stopping the chemical imbalances that cause brain cells to die, these all eventually lead straight back to protecting mitochondria as the cellular power source. Incidentally, any MMP-9 pharmaceutical strategy is possibly 10 to 15 years away from helping people as it can take a long time to gain government approval. Neurovive has been working 17 years on this – NeuroSTAT is currently in a phase II/III clinical study with human TBI patients – and they’re now “only” two to five years away from approval. Which is basically tomorrow in the pharmaceutical world.
If you’re interested, my article is in Pharmaceutical Formulation & Quality magazine and you can read the article online. It’s at www.pharmaquality.com and look in the archives in the August/September 2011 issue.
As for applications in boxing, football or any sport or injury where TBI is suspected, such as on the battlefield, once NeuroSTAT has been approved by the government, doctors would likely inject it right after an injury to begin protecting brain cells during the all-important first few days after the initial injury. Unfortunately, since it only protects living brain cells, it can’t help veterans, older boxers and others suffering the long-term after effects of brain cell loss, TBI and PTSD.
Eventually, though, the prospect is that every hospital emergency department will have a supply of this medicine on hand to take on the scourge of TBI which affects 1.7 million Americans every year. Happily, that future looks to be only a few years away.

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