Repetitive Low-Level Blast Exposure Alters Circulating Myeloperoxidase, Matrix Metalloproteinases, and Neurovascular Endothelial Molecules in Experienced Military Breachers
Shawn G. Rhind, Maria Y. Shiu, Catherine Tenn, Ann Nakashima, Rakesh Jetly, Venkata Siva Sai Sujith Sajja, Joseph B. Long, Oshin Vartanian
Abstract
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.