Low-intensity blast-induced mild traumatic brain injury : linking blast physics to biological outcomes

Abstract

Blast-induced mild traumatic brain injury (mTBI) is of particular concern among military personnel due to exposure to blast energy during military training and combat. The impact of primary low-intensity blast (LIB) mediated pathophysiology upon later neurobehavioral disorders has been controversial. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a LIB injury murine model exposed to open-field detonation of 350 g of high-energy explosive C4. The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 pounds per square inch (PSI) (46.6 kPa) at a 3-meter (m) distance from the center of the explosion, with no apparent impact / acceleration in exposed animals. We first characterized neuropathological and behavioral changes. Using transmission electron microscopy (TEM), we further identified multifocal neuronal damages, myelin sheath defects, mitochondrial abnormalities, and synaptic dysregulation after LIB injury. Next, we used quantitative proteomics, bioinformatics analysis, biochemical investigations to seek insights into the molecular mechanisms underlying the ultrastructural pathology. Results illustrated the alterations of mitochondrial, axonal, synaptic proteins in related signaling pathways. These observations uncover unique ultrastructural brain abnormalities, biochemical correlates, and associated behavioral changes due to LIB injury. Insights on the early pathogenesis of LIB-induced brain damages provide a template for further characterization of its chronic effects, identification of potential biomarkers and targets for intervention.