October 1, 2007
New Research Effort in Blast-Induced Neurotrauma
News stories about casualties in Iraq and Afghanistan have raised awareness of the damaging effects of traumatic brain injury and its high incidence among U.S. troops returning from those fronts.
But for I. Cernak, M.D., traumatic brain injury caused by explosions, or "blast-induced neurotrauma," has been the focus of her career since 1989. Biomedicine Business Area Executive D. Smith appointed Cernak APL's medical director in 2006, introducing a new research direction for the Lab. Her work breaks from the previously accepted dogma that the skull protects the brain from an explosion's primary blast wave of fast moving, high-pressure air.
Cernak now leads an effort to build a Hopkins-wide team of brain injury experts whose ambitious goals are to understand exactly how a blast wave affects the brain, develop a way to quickly and accurately detect brain injury, and to develop treatment.
A New Kind of Injury
For U.S. military troops in Iraq, explosive devices account for at least 60 percent of deaths and more than 70 percent of injuries, figures drastically higher than Americans have seen in all previous conflicts. Nearly six out of 10 casualties entering Walter Reed Medical Center have been diagnosed with some degree of traumatic brain injury.
"This is a new type of injury because of new types of explosives and better body armor," says Cernak. Body armor and helmets protect troops from injuries that in the past would have killed them, but their survival reveals that explosions can seriously harm the brain, even in the absence of life-threatening injuries.
An explosion heats and accelerates air molecules, causing a rapid increase in air pressure. The high-pressure blast wave lasts just a few thousandths of a second — about one third of the time it takes to blink an eye — but long enough to cause severe damage.
Air-containing organs such as the ears, lungs and gastrointestinal tract are most susceptible to the compressing and shearing effects of the rapid pressure change. Since the 1960s, it was believed the brain was vulnerable only to flying debris, concussive injury, or air bubbles forced from organs that can block the flow of blood.
In the late 1980s and early 1990s, Cernak saw all of these injuries while treating casualties at the Military Medical Academy in Belgrade, in what was then Yugoslavia. But she also saw patients with no obvious signs of injury to the head who nonetheless suffered debilitating symptoms. Months after exposure to a blast, they began to experience memory loss, headaches, confusion, an impaired sense of reality, reduced decision-making ability and more.
Frustrated that current medical knowledge could not explain the symptoms, Cernak volunteered to go into the battlefield. "I developed a clinical study," she says, "and took blood samples, sometimes within minutes of exposure." She also administered a post-traumatic stress disorder questionnaire, psychological tests and electroencephalograms (EEGs) to measure electrical activity in the soldiers' brains.
As her research eliminated various explanations for the neurotrauma, Cernak theorized that the primary blast wave creates oscillating waves in blood vessels that travel to the brain, stretching and damaging neural cells. The weakened cells no longer function as they should and the changes to their structure, biochemistry and gene expression lead to a cascade of problems that often results in cell death.
"In 1999, I presented my experimental and clinical findings at international congresses. Many thought it was crazy, impossible," she says. But since then, Cernak has gathered data from experiments conducted with colleagues in China, Australia, Sweden and elsewhere. They've proven that a brain physically shielded from a blast wave can still be injured by one, as the wave's kinetic energy is transferred by blood vessels from the torso or abdomen to the brain. Now, says Cernak, most neuroscientists accept the possibility that the primary blast wave causes neurotrauma.
"Brain injury research is a new focus area for the Lab," says M. McLoughlin, deputy executive for the Biomedicine Business Area. "But APL has been working on blast effects on the body for several years."
The Biomechanics Section uses a sensor-laden, artificial torso to model how internal organs react to blasts, and is now developing a head and neck that will help model what goes on inside a skull when it is exposed to a blast.
A prototype shock tube recreates the overpressure signature of a real explosion, using compressed air and a series of diaphragms. "The goal is to develop a six-foot diameter tube," says A. Merkle, of the National Security Technology Department. The full-scale tube will be unlike most of that size, which rely on explosives.
Cernak's work is funded through the Internal Research and Development program, but government investment in traumatic brain injury research is growing through the Defense Advanced Research Projects Agency, Office of Naval Research and the congressionally mandated Department of Defense Traumatic Brain Injury Multidisciplinary Research Consortium Award, run by the U.S. Army.
Cernak is glad to see the increased attention to and funding for the problem, but hopes that these efforts will move quickly so they might help today's warfighters. "I have always felt that soldiers are one of the most vulnerable populations in the world," she says. "I joined the Lab so that my research might have a more immediate impact on those who need it most."