Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel.

Objective: The purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms. Methods: Participants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay. Results: Serum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05). Conclusions: These findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.

Hearing Loss and Irritability Reporting Without Vestibular Differences in Explosive Breaching Professionals.

Background: Blast exposure is a potential hazard in modern military operations and training, especially for some military occupations. Helmets, peripheral armor, hearing protection, and eye protection worn by military personnel provide some acute protection from blast effects but may not fully protect personnel against cumulative effects of repeated blast overpressure waves experienced over a career. The current study aimed to characterize the long-term outcomes of repeated exposure to primary blast overpressure in experienced career operators with an emphasis on the assessment of hearing and vestibular outcomes. Methods: Participants included experienced "breachers" (military and law enforcement explosives professionals who gain entry into structures through controlled detonation of charges) and similarly aged and experienced "non-breachers" (non-breaching military and law enforcement personnel). Responses to a clinical interview and performance on audiological and vestibular testing were compared. Results: Hearing loss, ringing in the ears, irritability, and sensitivity to light or noise were more common among breachers than non-breachers. Breachers reported more combat exposure than non-breachers, and subsequently, memory loss and difficulty concentrating were associated with both breaching and combat exposure. Vestibular and ocular motor outcomes were not different between breachers and non-breachers. Conclusion: Hearing-related, irritability, and sensitivity outcomes are associated with a career in breaching. Future studies examining long-term effects of blast exposure should take measures to control for combat exposure.

Functional and Structural Neuroimaging Correlates of Repetitive Low-Level Blast Exposure in Career Breachers.

Combat military and civilian law enforcement personnel may be exposed to repetitive low-intensity blast events during training and operations. Persons who use explosives to gain entry (i.e., breach) into buildings are known as "breachers" or dynamic entry personnel. Breachers operate under the guidance of established safety protocols, but despite these precautions, breachers who are exposed to low-level blast throughout their careers frequently report performance deficits and symptoms to healthcare providers. Although little is known about the etiology linking blast exposure to clinical symptoms in humans, animal studies demonstrate network-level changes in brain function, alterations in brain morphology, vascular and inflammatory changes, hearing loss, and even alterations in gene expression after repeated blast exposure. To explore whether similar effects occur in humans, we collected a comprehensive data battery from 20 experienced breachers exposed to blast throughout their careers and 14 military and law enforcement controls. This battery included neuropsychological assessments, blood biomarkers, and magnetic resonance imaging measures, including cortical thickness, diffusion tensor imaging of white matter, functional connectivity, and perfusion. To better understand the relationship between repetitive low-level blast exposure and behavioral and imaging differences in humans, we analyzed the data using similarity-driven multi-view linear reconstruction (SiMLR). SiMLR is specifically designed for multiple modality statistical integration using dimensionality-reduction techniques for studies with high-dimensional, yet sparse, data (i.e., low number of subjects and many data per subject). We identify significant group effects in these data spanning brain structure, function, and blood biomarkers.