A Military-Relevant Model of Closed Concussive Head Injury: Longitudinal Studies Characterizing and Validating Single and Repetitive mTBI

Principal Investigator: SHEAR, DEBORAH
Institution Receiving Award: THE GENEVA FOUNDATION
Program: PH-TBI
Proposal Number: PT110545
Award Number: W81XWH-12-2-0134
Funding Mechanism: Applied Neurotrauma Research Award
Partnering Awards:
Award Amount: $2,324,065.00


The primary mission of military medicine is the care of injured soldiers. Combat-related traumatic brain injury (TBI) is one of the leading causes of military casualties as it persistently accounts for 20% to 25% of all battle-incurred injuries in the modern theatre of war. Likewise, worldwide TBI is a significant public health concern, where in the United States alone it affects over 1.5 million people each year. Because of sports injuries, automobile accidents, falls, etc., and with the escalation of the use of improvised explosion devices (IEDs) by our enemies as witnessed in the most recent military conflicts in Iraq and Afghanistan, there has been an increased awareness of closed head concussions, also commonly referred to as the mild TBI (mTBI) injury. The prevalence of this type of closed-head brain injury, estimated as afflicting over 300,000 deployed soldiers or approximately 30% of all deployed troops, has distinguished it as the "signature injury" of these military conflicts.

Despite the enormity of this medical problem and recognition of the importance for the need to quickly and accurately diagnose the event in the face of a limited clinical presentation (i.e., no obvious wounds to the head), objective diagnostic tools and knowledge about what occurs in the brain following this type of injury are limited. Of equal concern is our lack of understanding the impact of multiple concussions on the brain and its consequences on the long-term health of individuals. Ideally, any medical diagnosis, including concussion, would be based on objective criteria leading to a clear definition of the injurious changes that the brain has endured, and more importantly identify when the brain has completely healed. However, the closed head concussion/mTBI injury as we know it does not produce easily identified diagnostic markers of the injury and without the use conventional brain imaging techniques like CAT scans and/or MRIs available in all civilian trauma centers, medical diagnosis in a war zone is left to subjective clinical exams often made more difficult by the presence of other obvious serious injuries. Consequently, there is an urgent need to improve the diagnosis of a concussion in the austere combat environment and to be able to equivocally define under all conditions, i.e., civilian or military, children, young adults, and the elderly, when indeed the brain has healed from the concussion. Questions of when and how to treat and the critical decisions surrounding return to play (civilian sports) and return to duty (military combat commanders) remain unanswered.

In order to begin addressing this emerging medical crisis, we have developed a new concussive head impact injury model in rodents significantly relevant to the military. The model requires the subject to wear a Kevlar-type helmet (specially designed by our Army engineer colleagues) and has been demonstrated in seminal experiments to meet the "clinical" criteria of a concussion causing a highly reproducible mTBI. The focus of this research proposal is study this closed head mTBI in the context of a single concussion and multiple concussions, defining the cell biology, neurology (motor, memory, and emotional damage), and return to duty/return to play questions.