Study Links Explosions to Brain Disease in Military Vets

For the first 24 hours after an improvised explosive device (IED) was detonated nearby, the young soldier felt dizzy. He was unusually tired and his head throbbed with pain. Over the next two years, the headache became a daily curse, and the soldier became depressed, forgetful, inattentive, violent, and verbally abusive. Diagnosed with post-traumatic stress disorder (PTSD), he died three months later from a brain hemorrhage. He was 22.

When a BU-led research team probed the soldier’s brain, and the brains of three other blast-exposed vets from Iraq and Afghanistan who had suffered similar disabilities, they found them to be riddled with a protein associated with a degenerative brain disease in concussed professional athletes, chronic traumatic encephalopathy (CTE). Their study, published in the journal Science Translational Medicine May 16 connects blast exposure with CTE and with devastating neural and cognitive impairments. The researchers hope the study will help advance preventive and treatment measures for the military.

Lee Goldstein, a School of Medicine associate professor of psychiatry, neurology, ophthalmology, pathology, and laboratory medicine and a College of Engineering associate professor of biomedical engineering, is one of the study’s lead authors. He says the team, which examined the brains of three deceased high school and college football players and the brain of a professional wrestler, has confirmed that the signs of CTE in the athletes and in the blast-exposed vets are indistinguishable.

“We’ve found the basis for shell-shock,” says the other lead author, Ann McKee, a MED professor of neurology and pathology and a codirector of BU’s Center for the Study of Traumatic Encephalopathy (CSTE). “It’s terrifying when you think of the implications.”

Because three of the four vets whose brains were studied had suffered concussions prior to their military service, the researchers tested the apparent relationship of blasts to CTE by exposing anesthetized lab mice to a simulated explosion. “I can assure you that none of these mice had ever played football” or suffered other traumatic brain injury before the tests, Goldstein says. The team fashioned the laboratory detonation to be “comparable to a common IED fabricated from a 120-mm artillery round” and “within the reported range of typical explosives, blast conditions, and standoff distances associated with military blast injury.” They used high-speed video cameras to record the rapid movement of the mice’s heads during the simulated blast, hypothesizing that the blast’s violent shaking of the skull (the “bobblehead effect”) caused persistent brain injury.

The exposed mice developed brain tau, a protein associated with CTE, and other signs of the disease. They also suffered memory and learning problems—for example, they found it harder to escape from a maze than did a control set of mice. By contrast, mice exposed to a simulated blast with their heads immobilized did not suffer learning and memory impairments.

“The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related [traumatic brain injury] and CTE,” the researchers report. “Our results provide compelling evidence linking blast exposure to long-lasting brain injury. Specifically, our study raises concern that blast exposure may increase risk for later development of CTE” and associated behavioral impairments.

Next, Goldstein’s lab will try to learn “how one could mitigate this in the battlefield.”

Outside experts consulted by the New York Times say more research is necessary to persuade them of the blast-CTE link, but they also call the BU work an important step for other scientists who are exploring the possible connection. The Times reports that since 2001 more than 220,000 troops have suffered traumatic brain injury, “widely considered the precursor to CTE.” The BU results, if corroborated, raise the frightening possibility that many combat vets could be at risk for long-term neurological impairments, the paper notes.

The BU Alzheimer’s Disease Center and Center for the Study of Traumatic Encephalopathy provided the human brains for the study. With its brain bank (boxer “Irish” Micky Ward, the protagonist of the hit film The Fighter, is among many athletes from several sports who have pledged their brains to the bank after they die) and research tying head injuries to depression and dementia in retired athletes, the CSTE has garnered media attention and prodded rule changes by the National Football League.

Goldstein’s research team, from an array of academic and government institutions nationally, includes two others from BU. Both are codirectors, with McKee and former football player and professional wrestler Chris Nowinski, of the CSTE: Robert Cantu, a MED clinical professor of neurosurgery, and Robert Stern, a MED professor of neurology and neurosurgery.