Repeated Low-Level Blast Exposure: A Descriptive Human Subjects Study

Carr, Walter; Stone, James L.; Walilko, Tim; Young, Lee Ann; Snook, Tianlu Li; Paggi, Michelle E.; Tsao, Jack W.; Jankosky, Christopher; Parish, Robert; Ahlers, Stephen T.

doi:10.7205/milmed-d-15-00137

Cited by 93 publications

(72 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protocol was approved by the Naval Medical Research Center and Walter Reed Army Institute of Research Institutional Review Boards (NMCR#2011.0002; WRAIR#1796) (Carr et al, 2016). All participants provided informed consent prior to data collection.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

Self Cite

View full text Add to dashboard Cite

A unique cohort of military personnel exposed to isolated blast was studied to explore acute peripheral cytokine levels, with the aim of identifying blast-specific biomarkers. Several cytokines, including interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNFα) have been linked to pre-clinical blast exposure, but remained unstudied in clinical blast exposure. To address this gap, blood samples from 62 military personnel were obtained at baseline, and daily, during a 10-day blast-related training program; changes in the peripheral concentrations of IL-6, IL-10 and TNFα were evaluated using an ultrasensitive assay. Two groups of trainees were matched on age, duration of military service, and previous history of blast exposure(s), resulting in moderate blast cases and no/low blast controls. Blast exposures were measured using helmet sensors that determined the average peak pressure in pounds per square inch (psi). Moderate blast cases had significantly elevated concentrations of IL-6 (F1,60 =18.81, p < 0.01) and TNFα (F1,60 =12.03, p < 0.01) compared to no/low blast controls; levels rebounded to baseline levels the day after blast. On the day of the moderate blast exposure, the extent of the overpressure (psi) in those exposed correlated with IL-6 (r = 0.46, p < 0.05) concentrations. These findings indicate that moderate primary blast exposure results in changes, specifically acute and transient increases in peripheral inflammatory markers which may have implications for neuronal health.

show abstract

Section: Methodsmentioning

confidence: 99%

“…A questionnaire described in depth previously (Carr et al, 2016), was used to determine daily changes in symptoms including the following: irritability, feelings of depression or sadness, frustration, and feeling anxious or tense. Changes in reporting were compared between the groups.…”

Section: Methodsmentioning

confidence: 99%

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

Self Cite

View full text Add to dashboard Cite

show abstract

“…46 Typical exposures in this type of training are <1 psi. 47 For consideration of the large-magnitude blast exposure we recorded, we took the average symptom levels reported in days 1-6 and compared with the average from days 7 to 10, inclusive of the seventh day high-magnitude blast event. Similarly, for pre-post breaching course analyses, we analyzed symptoms that ‡10 subjects had when responding pre-vs. post-blast, where ''pre-''…”

Section: Dna Methylation and Transcriptional Changes Associated With mentioning

confidence: 99%

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers

Wang

Wilson

Mendelev

et al. 2020

Journal of Neurotrauma

Self Cite

View full text Add to dashboard Cite

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military ''breachers'' were exposed to controlled, lowlevel blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low versus high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise-related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre-versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ‡1.5), including UFC1 and YOD1 ubiquitin-related proteins, were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely after blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

show abstract

“…46 Typical exposures in this type of training are less than 1psi. 47 For consideration of the large magnitude blast exposure we recorded, we took the average symptom levels reported in days 1-6 and compared with the average from days 7-10, inclusive of the 7th day high magnitude blast event. Similarly, for pre-post breaching course analyses, we analyzed symptoms that ≥ 10 subjects had when responding prevs.…”

Section: Dna Methylation and Transcriptional Changes Associated With Acmentioning

confidence: 99%

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers

Wang

Wilson

Mendelev

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military "breachers" were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily selfreported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with chronic lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low vs. high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise related hearing loss.Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre-versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥ 1.5), including UFC1 and YOD1, ubiquitin-related proteins were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely following blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute lowlevel blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

show abstract

Repeated Low-Level Blast Exposure: A Descriptive Human Subjects Study

Cited by 93 publications

References 17 publications

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers

Contact Info

Product

Resources

About