BRIEF RESEARCH REPORT article
Front. Neurol.
Sec. Neurotrauma
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1589742
Impact of Prior Exposures on Biomarkers of Blast During Military Tactical Training
Provisionally accepted
Fatemeh Haghighi1,2*
Zhaoyu Wang1,2
Shengnan Sun1,2
Qingkun Liu1,2
Alis Askar Kranfli3
Jeffrey Nemes3Molly Sullan4,5Andrew Hoisington4,5Lisa A Brenner4,5
Maciej Skotak3Christina R Lavalle3Yongchao Ge1Walter Carr3- 1Icahn School of Medicine at Mount Sinai, New York, United States
- 2James J. Peters VA Medical Center, United States Department of Veterans Affairs, Bronx, New York, United States
- 3Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
- 4Rocky Mountain Regional VA Medical Center, VA Eastern Colorado Health Care System, Aurora, Colorado, United States
- 5University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
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Introduction: Blast injuries and subclinical effects are of significant concern among those Service Members (SMs) participating in military operations and tactical trainings. Studies of SMs repeatedly exposed during training find concussion-like symptomology with transient decrements in neurocognitive performance, and alterations in blood biomarkers. How prior mild TBI (mTBI) history interacts with low-level blast (LLB) exposure, however, remains unexplored, which we investigate in the present study, to identify interindividual biomarker changes from LLB exposures influenced by prior history of mTBI.Methods: Gene transcript and amyloid-beta (Aβ40 and Aβ42) protein levels were assayed using timeseries blood specimens collected at pre-blast, post (within ~1hr), and follow-up (~16hr) after LLB exposure for 30 SMs (age 30.3 ± 7.5) via RNA-seq and Single Molecule Array (SIMOA). Statistical models with timepoint and mTBI status interaction adjusted for age were used, and p-values adjusted for multiple testing.Results: We found enrichment of genes involved in blood brain barrier, inflammatory, and immune responses associated with blast exposure, with significant elevated expression of target genes amongst SMs with mTBI history. Levels of Aβ40 and Aβ42 did not differ pre-blast vs. post/follow-up LLB exposure when comparing SMs by prior mTBI history. Aβ40 and Aβ42 levels were significantly decreased in response to blast at the follow-up (~16hr) LLB exposure timepoint, concomitant with elevated expression of genes involved in amyloid-beta regulation and clearance in SMs with mTBI.Conclusions: Findings show inter-individual differences in biomarker levels following exposures to blast that may be attributed to prior mTBI history.
Keywords: Blast Overpressure, MTBI, Gene Expression, biomarker, breacher, Amyloid beta
Received: 19 Mar 2025; Accepted: 23 Apr 2025.
Copyright: © 2025 Haghighi, Wang, Sun, Liu, Kranfli, Nemes, Sullan, Hoisington, Brenner, Skotak, Lavalle, Ge and Carr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fatemeh Haghighi, Icahn School of Medicine at Mount Sinai, New York, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.