Neurological Effects of Repeated Blast Exposure in Special Operations Personnel

Abstract

Exposure to blast overpressure has been a pervasive feature of combat-related injuries. Studies exploring the neurological correlates of repeated low-level blast exposure in career “breachers” demonstrated higher levels of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 and decreases in IL-10 within brain-derived extracellular vesicles (BDEVs). The current pilot study was initiated in partnership with the U.S. Special Operations Command (USSOCOM) to explore whether neuroinflammation is seen within special operators with prior blast exposure. Data were analyzed from 18 service members (SMs), inclusive of 9 blast-exposed special operators with an extensive career history of repeated blast exposures and 9 controls matched by age and duration of service. Neuroinflammation was assessed utilizing positron emission tomography (PET) imaging with [ 18 F]DPA-714. Serum was acquired to assess inflammatory biomarkers within whole serum and BDEVs. The Blast Exposure Threshold Survey (BETS) was acquired to determine blast history. Both self-report and neurocognitive measures were acquired to assess cognition. Similarity-driven Multi-view Linear Reconstruction (SiMLR) was used for joint analysis of acquired data. Analysis of BDEVs indicated significant positive associations with a generalized blast exposure value (GBEV) derived from the BETS. SiMLR-based analyses of neuroimaging demonstrated exposure-related relationships between GBEV, PET-neuroinflammation, cortical thickness, and volume loss within special operators. Affected brain networks included regions associated with memory retrieval and executive functioning, as well as visual and heteromodal processing. Post hoc assessments of cognitive measures failed to demonstrate significant associations with GBEV. This emerging evidence suggests neuroinflammation may be a key feature of the brain response to blast exposure over a career in operational personnel. The common thread of neuroinflammation observed in blast-exposed populations requires further study.

Impact of repeated blast exposure on active-duty United States Special Operations Forces

“…Thus, our TSPO PET findings within the rACC do not distinguish specific changes in neuroimmune function from broader alterations in cellular metabolism. A key future direction will be to elucidate the pathophysiological mechanisms and temporal dynamics underlying the relationship between neuroimmune function, cellular metabolism, and astroglial scarring at the gray-white matter junction, particularly given emerging evidence of neuroinflammation in SOF personnel ( 23 ).…”

Neural Network Correlates of Apathy, Disinhibition, and Executive Dysfunction in Active-Duty United States Special Operations Forces

“…13 Interestingly, in a different cohort of active-duty SOF, higher blast exposure was associated with increased TSPO signal in the salience network. 15 The discrepancy in findings across these two studies 13,15 may have been due to the use of a different tracer (i.e., [18F]DPA-714), a different statistical analytic approach (i.e., applying dimensionality reduction before testing the association between biomarkers and blast exposure), or a different study design (i.e., comparing blast-exposed special operators to non-exposed matched controls). Overall, the present work illustrates the potential neurobehavioral consequences of network-level disruptions in a population heavily exposed to blast and blunt head trauma.…”

Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging

“…In a study by Trotter et al [ 71 ], Veterans with a history of blast exposure not only showed a similar graded association via DTI but also demonstrated a more rapid decline in white matter integrity with age compared to unexposed individuals, indicating that cumulative blast exposure may contribute to an accelerated aging process. A recent study by Stone et al [ 34 ] supports these findings, revealing that special operators with repeated LLB exposure show elevated PET-neuroinflammation, a characteristic of neurovascular dysfunction and contributor to the progression of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [ 72 ].…”

“…The cell-to-cell communication is vital for maintaining BBB integrity and regulating CBF [ 32 , 33 ]. While it is difficult to isolate the pathological effects of LLB in humans, studies focused on cumulative wall breaching and mbTBI have analyzed neuroimaging and serum biomarkers to better understand the mechanisms of blast-induced brain injury [ 13 , 29 , 34 ]. Simultaneously, numerous preclinical studies have been performed to study primary blast overpressure as the main experimental variable.…”