Some Clues to the Prevention and Treatment of TBI

by Kayt Sukel

January 22, 2013

On April 13, 2011, Oliver Hughes was on a mounted patrol in Afghanistan when his vehicle hit an improvised explosive device (IED). The major impact of the blast occurred right under his seat, crumpling the floor plates beneath the dashboard, pinning his legs below the knees. The force of the blast also slammed his head forward, shattering the tracker screens in front of him. Hughes’ physical injuries were severe—his right leg was crushed and the left leg was torn off below the knee. But he also suffered more invisible wounds. More than a year after his injury, Hughes’ wife, Megan, reports that he shows classic symptoms of a traumatic brain injury (TBI), with difficulties focusing on tasks and remembering appointments.

Stories like Hughes’ are not that uncommon. And with the Department of Defense (DoD) reporting that tens of thousands of U.S. military personnel will be diagnosed with TBI each year, neuroscientists are trying to identify new compounds that could prevent the chronic cognitive and behavioral problems that often follow head injury.

Treatment at the Point of Injury

Since the start of the wars in Iraq and Afghanistan, the number of reported TBI cases in the U.S. military has jumped nearly five-fold.

“Currently, we’re seeing about 30,000 service members each year who have sustained a concussion or traumatic brain injury,” says Donald Marion, a neurosurgeon and clinical consultant at the Defense and Veterans Brain Injury Center. “Fortunately, the majority of those individuals end up doing fairly well. But many will suffer long-term consequences of their injury.”

Those consequences may include cognitive problems with memory and attention, personality changes, anxiety and depressive disorders, and even thoughts of suicide. While it remains unclear what types of head injuries will result in what types of problems, research does suggest that the earlier a potential injury is diagnosed and treated, the better the outcome will be. This is why, Marion says, the DoD is using a new decision-tree method, called the Military Acute Concussion Evaluation (MACE), to evaluate service members suspected of having any type of head injury.

“Groups of service members out in the field will not have a medical doctor with them. They’ll have a Corpsman or a Combat Medic serving with them. While these medics receive intensive training, they can’t be expected to know all the same things that a neurologist might know,” says Marion. “The MACE tool lets them just go through the decision-tree and evaluate any service member who has been around an IED or blast and determine whether or not they’ve had a concussion and how severe that concussion might be.”

Still, Marion concedes, there are many cases where service members sustain multiple serious injuries—and the medic’s job is to stabilize the patient for transfer, not assess their cognitive skills. In Hughes’ case, his TBI evaluation did not occur until about two weeks after his initial injury—after he was already transferred out of Afghanistan and on heavy pain medication for his injuries. That's a missed opportunity: If researchers could identify novel drugs or compounds that could be given within four to six hours after injury, it’s possible that the long-term consequences of head injury might be avoided altogether.

The Promise of Anatabine

David Loane, a scientist at the Center for Shock, Trauma, and Anesthesiology Research (STAR) at the University of Maryland, says new research suggests that TBI results in chronic microglia activation, which changes the brain’s white matter. “We’re beginning to see that microglia activation and neuroinflammation is a chronic pathology that’s associated with TBI,” he says. “It’s a progressive and chronic disorder that continues indefinitely after the initial traumatic insult.”

Given that inflammatory pathways are so significantly affected, Fiona Crawford, a researcher at the Roskamp Institute, wondered if some of the long-term damage, particularly memory problems, could be avoided by using a compound that dampens the brain’s natural inflammatory response. She and her colleagues had already found evidence that anatabine, a dietary supplement found in tobacco leaves, tomatoes, and eggplant, was a powerful anti-inflammatory agent.

The group compared mice with brain injuries after being given anatabine versus a placebo. When they were put into the Barnes Maze task, a tool to measure spatial learning and memory, the mice who had received the anatabine after TBI performed as well as uninjured mice. Crawford presented the research at the Society for Neuroscience's annual meeting in 2012.

“The anatabine appears to mitigate the neurobehavioral deficits that were the consequence of the head injury,” says Crawford. “It makes sense, in terms of the fact that we know that inflammation is a big part of the response to head injury and that, by mitigating some of the detrimental effects of neuroinflammation, we might be able to improve the behavioral outcomes.”

Moving Forward

Crawford cautions that her data is very preliminary, but she believes it holds great promise. She plans to continue testing anatabine, hoping it will eventually make it to human clinical trials. Still, while the data are interesting, Loane says, it pays to be cautious about what such supplements can actually do.

“There’s never going to be a magic bullet kind of approach for therapy when it comes to head injuries because there are so many different second injury mechanisms that occur after the initial impact,” says Loane. “The biggest challenge in treating TBI is the heterogeneity of those secondary injuries. There are multiple pathways that are affected.”

Still, Megan Hughes, wife of Oliver Hughes, is hopeful that researchers will find something that can ease, if not prevent, the long-term effects of traumatic brain injury—especially for people like her husband.

“I think it’s important for them to be treated in theater, not to wait. [Oliver’s] definitely lost something,” she says. “And the loss of brain function is scarier to him than the loss of his limb. I see so many soldiers come back different people. They come back so different and their families fall apart. If supplements and immediate treatment could help, we need to know that. We need that research.”