Causes and Consequences of Mild Blast-Induced Traumatic Brain Injury: From Biomechanics to Behavior

Author: Race, Nicholas Stephen (Purdue University) (2017), Advisor: Shi, Riyi

Blast-induced traumatic brain injury (b-TBI) is regarded as the ‘signature injury’ of modern violent conflict. It has been repeatedly linked to numerous neuropathologies, which are common among military personnel and Veterans. The complexities of blast exposure have left the pathophysiologic mechanisms underlying blast-induced alterations to brain structure, function, and resultant behavioral changes ambiguous. This is particularly true for mild blast injuries, which are acutely subclinical and often undiagnosed. As a result, the field has struggled to achieve translationally-relevant findings with potential to positively impact preventative, diagnostic, prognostic, or treatment paradigms. A major obstacle preventing such progress has been difficulty crossing scales and disciplines. Understanding b-TBI requires integration of numerous disciplines across multiple scales, ranging from trauma biomechanics and systems neuroscience to neural physiology and molecular biology to neurobehavior and psychosocial processing. To this end, the authors developed a research platform capable of tackling the multifaceted mysteries of b-TBI head on. This thesis work details development of a collaborative, multi-disciplinary research program capable of simultaneously investigating brain injuries from blast through the lenses of biomechanics, molecular biology, neurophysiology, neuroimaging, and behavior. In this model, the authors observed direct evidence of mechanical perturbation of the brain by mild blasts, demonstrated the ability to leverage noninvasive neurophysiological, biochemical, and neuroimaging assessments to separate injured from uninjured subjects, and observed a key role for oxidative stress in leading to altered neural function and behavior after mild b-TBI. Overall, the results suggest acute therapeutic interventions targeting oxidative stress and noninvasive evoked potential neuromonitoring have high translational potential.