Individualized Medicine in a Gyrencephalic Model of TBI Polytrauma Through the Continuum of Care

BACKGROUND: Advancements in combat casualty care for traumatic brain injury (TBI) have greatly improved survival and treatment success rates during recent armed conflicts. Damage control resuscitation, delayed wound closure, tourniquets, and rapid evacuation for damage control surgery are examples of those observations contributing to improved care.

Military casualties face numerous complications to their care that are not commonly seen in civilian medical practice. These include the type and severity of injuries, as well as combat- related limitations on the care that can be provided in the field and the potentially prolonged delays to definitive care, including the possibility of prolonged aeromedical evacuation with its associated unique environmental stressors. However, most treatment strategies are based on standard protocols which lack the subtlety to account for patient-specific differences in response to therapy, thus resulting in missed opportunities for improved outcomes at the individual patient level. This study aims to identify strategies to improve outcomes by identifying predictors of an individual's response to injury and to environmental factors, such as air transport, with the goal of optimizing personalized treatment strategies. Results from this study will provide a knowledge that may help develop improved treatment of our wounded warriors.

OBJECTIVES: The purpose of this study is to identify strategies to improve outcomes associated with TBI and hemorrhagic shock (HS) by identifying biomarkers predictive of an individual's response to injury and to environmental factors (simulated prolonged en route care) with the goal of optimizing individual treatment strategies.

STUDY DESIGN: The research goals will be accomplished in three phases using an animal (the ferret) that has a brain with a complex surface that is more like a human brain than that of a rat or mouse.

Phase 1 will characterize TBI+HS in a ferret model of TBI and severe hemorrhage. It will identify characteristics (blood, CSF, brain tissue and neuroimaging biomarkers) that predict an individual's response to injury. Phase 2 will assess the effects of simulated flight (hypobaria) on the individual's response to injury and identify the best evacuation strategies for the individual patient. Phase 3 will channel knowledge gained from Phases 1 and 2 into improving individualized treatment approaches. Results from Phases 1 and 2 will guide selection of promising therapies for further testing in Phase 3.

These experiments will be conducted as a collaborative effort among three laboratories: The Surgical Critical Care Initiative (SC2i) at the Uniformed Services University of the Health Sciences (USU), The Naval Medical Research Center (NMRC), and The University of Virginia (UVA).

IMPACT: Result from this study will aid in the improvement of precision trauma care and casualty transport of the individual combat casualty.