Seau's brain could hold clues about NFL injuries' impacts 

click to enlarge New England Patriots Junior Seau speaks to reporters before training at the Oval Cricket Ground ahead of their NFL game against Tampa Bay Buccaneers in London in this October 23, 2009 file photograph. TMZ is reporting retired NFL star Junior Seau is dead in his home in Oceanside, California. - REUTERS/LUKE MACGREGOR/FILES
  • REUTERS/Luke MacGregor/Files
  • New England Patriots Junior Seau speaks to reporters before training at the Oval Cricket Ground ahead of their NFL game against Tampa Bay Buccaneers in London in this October 23, 2009 file photograph. TMZ is reporting retired NFL star Junior Seau is dead in his home in Oceanside, California.

When 300-pound professional football players repeatedly slam into each other like runaway freight trains, what impact does that have on their brains?

To find out, researchers who study sports-related injuries are examining the brains of former National Football League players like Junior Seau, 43, who committed suicide on Wednesday. They are trying to determine what, if any, long-term effect sports-related head injuries can have on players and whether damage caused by repeated jarring blows could have contributed to Seau's and other players' deaths.

Seau's family agreed to donate his brain to science after he shot himself in the chest this week. His death was at least the third suicide by a former NFL player since February 2011, when 50-year-old former Chicago Bears defensive back Dave Duerson shot himself in the chest and left a note asking that his brain be studied.

More than 1,500 former football players have sued the NFL over head injuries, and accused the league of concealing links between football and brain injuries. The NFL disputes those allegations, and said it has taken steps to protect players.

Neurosurgeon James Johnston of the University of Alabama at Birmingham said NFL players "have a higher rate of depression, substance abuse, and dementia compared to the general population, which may be connected to head impacts."

A standard autopsy, which a medical examiner in San Diego County conducted on S eau Thursday, does not reveal whether a player sustained the kind of permanent brain injuries that typically follow concussions, said Dr. David Hovda, professor of neurosurgery at the University of California, Los Angeles. A neuropathologist, ideally one with experience studying the brains of former athletes, must conduct the exam.

Two centers specialize in studying the brains of former athletes. The Brain Injury Research Institute in West Virginia has examined those of former NFL players Mike Webster, Justin Strzelczyk, Terry Long, and Andre Waters, among others. Boston University's Center for the Study of Traumatic Encephalopathy has studied the brains of professional football players Lou Creekmur, John Grimsley, Thomas McHale, and dozens more.

"In a weird way, we wish we didn't have to do this research," Garrett Webster, BIRI's family liaison, told Reuters. BIRI and BU are both trying to obtain Seau's brain for research, but it could go to another group, he said.

Boston University declined to comment on Seau's case or grant interviews with its scientists.

A year ago, the BU center released a report on its analysis of Duerson's brain. He was suffering from chronic traumatic encephalopathy, BU center co-director Ann McKee said in last year's report. That made him the 14th of 15 ex-NFL players studied by her group to be diagnosed with the condition. The damage was greatest in areas of the brain that involved in impulse control, emotion and memory.

'BOXER'S DEMENTIA'

Chronic traumatic encephalopathy is the formal name given to brain damage caused by concussions, but is known outside the doctor's office as boxer's dementia. It is a progressive, neurodegenerative syndrome caused by blunt force trauma to the head causing the brain to rapidly accelerate and decelerate, or slam against the skull.

"Repeated concussions and even sub-concussions from contact sports may lead to long-term cognitive and pathologic changes," Alabama's Johnston said.

Based on research on how sports concussions and near-concussions, called "sub-concussive injuries," affect the brain, a neuropathology examination would look for several telltale signs in Seau's, said Hovda: decreases in overall brain volume and in the volume of specific regions; the presence of a protein called tau that is also found in patients with Alzheimer's disease; changes in the white matter that connect neurons; and changes in the receptors by which neurochemicals act in the brain.

Suffering multiple concussions cause the brain to lose volume more quickly than it does otherwise (brains shrink with age), Hovda said. By slicing the brain, a neuropathologist can make precise measurements of its internal structures.

After concussions, the frontal cortex - located just behind the forehead and responsible for such "executive functions" as planning, judgment, and impulse control - tends to shrink more than other regions. That can cripple the brain's ability to control impulsivity, Hovda said, which may make suicide more likely.

Concussions can also cause a loss of white matter, the highways that allow neurons (gray matter) to communicate. As a result, "parts of the brain become disconnected," Hovda said.

Studies have shown that among the regions most likely to lose white matter is the corpus callosum. This is the fat bundle of neurons that connects the right side of the brain to the left. Since the left and right brain have somewhat different functions, the result can be, for instance, an inability to process emotions verbally. "It becomes difficult to put into words what you're feeling," Hovda said.

CHANGES AKIN TO ALZHEIMER'S DISEASE

Another common consequence of concussions and sub-concussive injuries is a profusion in the brain of a protein called tau. Also found in the brains of Alzheimer's patients, tau turns neurons into the equivalent of cold spaghetti: stuck together and dysfunctional. Eventually, tau kills neurons. The result is typically memory impairment, emotional instability, erratic behavior, depression, and problems with impulse control.

Tau cannot be seen on a standard autopsy, but special stains can turn tau a bright color, allowing it to be seen in brain slices, Hovda said.

Neurologists are mystified about why a mechanical injury like a concussion should cause this biochemical change. But studies of the brains of ex-NFL players by neuropathologists at the BU center have found this "tauopathy."

Finally, concussions and similar brain injuries alter the brain's receptors. Receptors are molecules that act as locks into which the "keys," or neurotransmitters, fit. When neurotransmitters dock with a receptor, two neurons communicate. When receptors change, that communication is impaired.

"After a brain injury, receptors are altered in a way that makes them less sensitive to neurotransmitters," as if someone stuck gum in the keyhole, Hovda said. "One result can be post-traumatic depression."

The altered receptors can also cause the brain to become less sensitive to neurotransmitters that quiet brain activity. "You can become disinhibited, which can cause impulsivity," Hovda said. "Or you can become very emotional, becoming angry or frustrated very easily."

An estimated 3.8 million athletes in the United States, from children to professionals, suffer a concussion every year, according to the U.S. Centers for Disease Control and Prevention.

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