Ann Nakashima

Repeated exposure to low-level blast overpressure, frequently experienced during explosive breaching and heavy weapons use in training and operations, is increasingly recognised as a serious risk to the neurological health of military personnel. Although research on the underlying pathobiological mechanisms in humans remains limited, this study investigated the effects of such exposure on circulating molecular biomarkers associated with inflammation, neurovascular damage, and endothelial injury. Blood samples from military breachers were analysed for myeloperoxidase (MPO), matrix metalloproteinases (MMPs), and junctional proteins indicative of blood–brain barrier (BBB) disruption and endothelial damage, including occludin (OCLN), zonula occludens-1 (ZO-1), aquaporin-4 (AQP4), and syndecan-1 (SD-1). The results revealed significantly elevated levels of MPO, MMP-3, MMP-9, and MMP-10 in breachers compared to unexposed controls, suggesting heightened inflammation, oxidative stress, and vascular injury. Increased levels of OCLN and SD-1 further indicated BBB disruption and endothelial glycocalyx degradation in breachers. These findings highlight the potential for chronic neurovascular unit damage/dysfunction from repeated blast exposure and underscore the importance of early targeted interventions—such as reducing oxidative stress, reinforcing BBB integrity, and managing inflammation—that could be essential in mitigating the risk of long-term neurological impairment associated with blast exposure.

Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers (n = 18) with extensive blast exposure against unexposed military controls (n = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG (p < 0.001) and anti-PIT IgG (p < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic–pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood–brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups.