Low-level Blast Research Articles

Long-Term Effects of Low-Level Blast Exposure and High-Caliber Weapons Use in Military Special Operators.

Chronic low-level blast exposure has been linked with neurological alterations and traumatic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often associated with TBI. The purpose of this study was to determine whether long-term operators of low-level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing task using an eye tracker and completed a concussion assessment questionnaire. The participants were split into a blast exposure group and control group. The blast exposure group had a history of exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences in SPEM, saccades, and fixations between the blast exposure group and control group. The blast exposure group’s eye movements were slower, stopped at more frequent points when following a target, traveled further from the target in terms of both speed and direction, and showed higher rates of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on the concussion assessment questionnaire. Military special operators exposed to long-term low-level blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to controls. These findings further our understanding of the impact of long-term low-level blast exposure on the oculomotor behavior of military special operators and may inform practical implications for military training.

Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel.

ObjectiveThe purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms.MethodsParticipants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay.ResultsSerum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05).ConclusionsThese findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.

Perspectives on Development of Measures to Estimate Career Blast Exposure History in Service Members and Veterans.

The Department of Defense (DOD) has recently prioritized the investigation of the acute and chronic adverse brain health and performance effects of low-level blast (LLB) generated by the use of weapons systems. While acute exposure can be quantified by sensor technology, career exposure has no widely accepted and validated measure for characterization. Currently, distinct research groups are developing and validating four promising measures to estimate career blast exposure history: the Salisbury Blast Interview, Blast Exposure Threshold Survey, Blast Ordnance and Occupational Exposure Measure, and the Blast Frequency and Symptom Severity. Each measure offers an assessment of blast history that is uniquely beneficial to addressing specific research questions. However, use of divergent strategies is not efficient to accelerate the field's understanding of the impact of career exposure and Service-connected health outcomes. As a DOD-wide solution, collaboration across these groups is required to develop a tool(s) that can be standardized across research studies and, ultimately, pared down to be implemented in clinical settings. Here, we overview the current four measures and provide a perspective on the way forward for optimization and/or combination in support of this solution.

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

Occupational Risk of Low-Level Blast Exposure and TBI-Related Medical Diagnoses: A Population-Based Epidemiological Investigation (2005-2015).

Because traumatic brain injury (TBI)—most often caused by exposure to high-level blast (HLB)—is a leading cause of medical evacuations of deployed U.S. service members in recent conflicts, researchers seek to identify risk factors for TBI. Previous research using self-reported data has identified low-level blast (LLB) as one such risk factor and suggests an association with susceptibility to and symptoms associated with TBI. This article presents a population-based study of all branches of military service that examines the association between occupational risk for LLB and both clinically diagnosed TBIs—from concussions to severe and penetrating TBIs—and conditions commonly comorbid with concussion. Using archival medical and career records from >2 million service members between 2005–2015, this work demonstrates that occupational risk of LLB is associated with any TBI, mild TBI, moderate TBI, cognitive problems, communication problems, hearing problems, headaches, any behavioral health condition, anxiety, drug abuse/dependence, alcohol abuse/dependence, delirium/dementia, posttraumatic stress disorder, post-concussive syndrome, tinnitus, fatigue, and migraines. Understanding the full scope of the effects of LLB on service members will help ensure the health and readiness of service members and may influence both military policy and clinical practice guidelines for blast-induced injuries.

Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes

Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness. rLLB does not display overt pathological symptoms; however, earlier studies report chronic neurocognitive changes such as altered mood, irritability, and aggressive behavior, all of which may be caused by subtle neuropathological manifestations. Current animal models of rLLB for investigation of neurobehavioral and neuropathological alterations have not been adequate and do not sufficiently represent rLLB conditions. Here, we developed a rat model of rLLB by applying controlled low-level blast pressures (<10 psi) repeated successively five times to mimic the pressures experienced by service members. Using this model, we assessed anxiety-like symptoms, motor coordination, and short-term memory as a function of time. We also examined levels of superoxide-producing enzyme NADPH oxidase, microglial activation, and reactive astrocytosis as factors likely contributing to these neurobehavioral changes. Animals exposed to rLLB displayed acute and chronic anxiety-like symptoms, motor and short-term memory impairments. These changes were paralleled by increased microglial activation and reactive astrocytosis. Conversely, animals exposed to a single low-level blast did not display significant changes. Collectively, this study demonstrates that, unlike a single low-level blast, rLLB exerts a cumulative impact on different brain regions and produces chronic neuropathological changes in so doing, may be responsible for neurobehavioral alterations.

Transcranial Laser Therapy Does Not Improve Cognitive and Post-Traumatic Stress Disorder-Related Behavioral Traits in Rats Exposed to Repetitive Low-Level Blast Injury.

Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Transcranial laser therapy (TLT) uses low-power lasers emitting light in the far- to near-infrared ranges. Beneficial effects of TLT have been reported in neurological and mental-health–related disorders in humans and animal models, including TBI. Rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits. We tested whether TLT treatment could reverse these traits. Rats received a 74.5-kPa blast or sham exposures delivered one per day for 3 consecutive days. Beginning at 34 weeks after blast exposure, the following groups of rats were treated with active or sham TLT: 1) Sham-exposed rats (n = 12) were treated with sham TLT; 2) blast-exposed rats (n = 13) were treated with sham TLT; and 3) blast-exposed rats (n = 14) were treated with active TLT. Rats received 5 min of TLT five times per week for 6 weeks (wavelength, 808 nm; power of irradiance, 240 mW). At the end of treatment, rats were tested in tasks found previously to be most informative (novel object recognition, novel object localization, contextual/cued fear conditioning, elevated zero maze, and light/dark emergence). TLT did not improve blast-related effects in any of these tests, and blast-exposed rats were worse after TLT in some anxiety-related measures. Based on these findings, TLT does not appear to be a promising treatment for the chronic cognitive and mental health problems that follow blast injury.

Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.

Infrasound signature measurements for U.S. Army infantry weapons during training

United States Military personnel are exposed to blast overpressure from a variety of sources during training and military operations. While it is known that repeated exposure to high-level blast overpressure may result in concussion like symptoms, the effect of repeated exposure to low-level blast overpressure is not well understood yet. Impulsive acoustic sources such as pressure waves generated by explosions, artillery launches, and rocket launches are typically characterized by a broadband energy distribution with resulting pressure measurements that exhibit frequency components well into the infrasound range. This study focused on data acquired in the audible and infrasound range during infantry weapons training for machine gun, grenade launcher and rocket fire events. Time, frequency and time-frequency analysis are used to quantify infrasound intensity for each event type. High resolution time-frequency analysis using the synchrosqueezed wavelet transform is used to precisely quantify energy content in the lowest frequency range. Preliminary results indicate that data collected from these weapon systems exhibited a large amount of infrasound in the range between 2 and 20 Hz. This energy can couple directly with the human body and in case of repeated exposures this coupling can include altering of physiological processes.

Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (−0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p’s > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

Repetitive Low-level Blast Exposure and Neurocognitive Effects in Army Ranger Mortarmen.

Occupational exposure to repetitive, low-level blasts in military training and combat has been tied to subconcussive injury and poor health outcomes for service members. Most low-level blast studies to date have focused on explosive breaching and firing heavy weapon systems; however, there is limited research on the repetitive blast exposure and physiological effects that mortarmen experience when firing mortar weapon systems. Motivated by anecdotal symptoms of mortarmen, the purpose of this paper is to characterize this exposure and its resulting neurocognitive effects in order to provide preliminary findings and actionable recommendations to safeguard the health of mortarmen. In collaboration with the U.S. Army Rangers at Fort Benning, blast exposure, symptoms, and pupillary light reflex were measured during 3 days of firing 81 mm and 120 mm mortars in training. Blast exposure analysis included the examination of the blast overpressure (BOP) and cumulative exposure by mortarman position, as well as comparison to the 4 psi safety threshold. Pupillary light reflex responses were analyzed with linear mixed effects modeling. All neurocognitive results were compared between mortarmen (n = 11) and controls (n = 4) and cross-compared with blast exposure and blast history. Nearly 500 rounds were fired during the study, resulting in a high cumulative blast exposure for all mortarmen. While two mortarmen had average BOPs exceeding the 4 psi safety limit (Fig. 2), there was a high prevalence of mTBI-like symptoms among all mortarmen, with over 70% experiencing headaches, ringing in the ears, forgetfulness/poor memory, and taking longer to think during the training week (n ≥ 8/11). Mortarmen also had smaller and slower pupillary light reflex responses relative to controls, with significantly slower dilation velocity (P < 0.05) and constriction velocity (P < 0.10). Mortarmen experienced high cumulative blast exposure coinciding with altered neurocognition that is suggestive of blast-related subconcussive injury. These neurocognitive effects occurred even in mortarmen with average BOP below the 4 psi safety threshold. While this study was limited by a small sample size, its results demonstrate a concerning health risk for mortarmen that requires additional study and immediate action. Behavioral changes like ducking and standing farther from the mortar when firing can generally help reduce mortarmen BOP exposure, but we recommend the establishment of daily cumulative safety thresholds and daily firing limits in training to reduce cumulative blast exposure, and ultimately, improve mortarmen's quality of life and longevity in service.

Repetitive Low-Level Blast Exposure Improves Behavioral Deficits and Chronically Lowers Aβ42 in an Alzheimer Disease Transgenic Mouse Model.

Public awareness of traumatic brain injury (TBI) in the military increased recently because of the conflicts in Iraq and Afghanistan where blast injury was the most common mechanism of injury. Besides overt injuries, concerns also exist over the potential adverse consequences of subclinical blast exposures, which are common for many service members. A TBI is a risk factor for the later development of neurodegenerative diseases, including Alzheimer disease (AD)-like disorders. Studies of acute TBI in humans and animals have suggested that increased processing of the amyloid precursor protein (APP) toward the amyloid beta protein (Aβ) may explain the epidemiological associations with AD. In a previous study, however, we found in both rat and mouse models of blast overpressure exposure that rather than increasing, rodent brain Aβ42 levels were decreased after acute blast exposure. Here we subjected APP/presenilin 1 transgenic mice (APP/PS1 Tg) to an extended sequence of repetitive low-level blast exposures (34.5 kPa) administered three times per week over eight weeks. If initiated at 20 weeks of age, these repetitive exposures, which were designed to mimic human subclinical blast exposures, reduced anxiety and improved cognition as well as social interactions in APP/PS1 Tg mice, returning many behavioral parameters in APP/PS1 Tg mice to levels of non-transgenic wild type mice. Repetitive low-level blast exposure was less effective at improving behavioral deficits in APP/PS1 Tg mice when begun at 36 weeks of age. While amyloid plaque loads were unchanged, Aβ 42 levels and Aβ oligomers were reduced in the brain of mice exposed to repetitive low-level blast exposures initiated at 20 weeks of age, although levels did not directly correlate with behavioral parameters in individual animals. These results have implications for understanding the nature of blast effects on the brain and their relationship to human neurodegenerative diseases.

The Persistence of Blast- Versus Impact-Induced Concussion Symptomology Following Deployment.

To examine the persistence of concussion-related symptoms following injury as a function of mechanism of injury (high-level blast [HLB] vs impact) and low-level blast (LLB) exposure among Marines. Upon return from deployment and approximately 6 months later, respectively, Marines completed the Post-Deployment Health Assessment and Post-Deployment Health Re-Assessment in an operational or clinic setting. Data from active duty enlisted Marines who completed both assessments (n = 102 075) and who reported a potentially mild traumatic brain injury (mTBI)-inducing event and completed an mTBI screen (n = 8106) were analyzed. This was a retrospective cohort study of Marines deployed between 2008 and 2012. Marines were categorized into groups with relatively high versus low risk for occupational risk of LLB exposure. A mixed model analysis of variance was used to examine the number of symptoms Marines reported experiencing during deployment as a function of probable concussion, HLB exposure, occupational risk, type of symptom, and time of measurement. Self-reported deployment exposures including HLB, probable mTBIs, and occupational risk of LLB exposure were identified. Outcomes included the proportion of neurological, musculoskeletal, and immunological symptoms for which Marines reported seeking care during and following deployment were analyzed. Probable HLB-induced mTBIs (vs impact-induced) were associated with significantly more neurological symptoms at return from deployment and approximately 6 months later. Although symptom reporting decreased at statistically equivalent rates regardless of mechanism of injury, those with a probable HLB-induced concussion continued to report elevated symptomology post-deployment. Additionally, Marines with probable concussion working in occupations with LLB exposure reported elevated levels of persistent neurological symptoms. Both HLB and LLB exposure were associated with neurological symptoms that persisted following deployment. These findings suggest that blast-induced brain injuries may be fundamentally different from impact-induced injuries, and that additional screening and symptomatic treatment for blast-exposed patients may be warranted.

Getting on the Same Page: Consolidating Terminology to Facilitate Cross-Disciplinary Health-Related Blast Research.

The consequences of blast exposure (including both high-level and low-level blast) have been a focal point of military interest and research for years. Recent mandates from Congress (e.g., National Defense Authorization Act for Fiscal Year 2018, section 734) have further accelerated these efforts, facilitating collaborations between research teams from a variety of disciplinary backgrounds. Based on findings from a recent scoping review, we argue that the scientific field of blast research is plagued by inconsistencies in both conceptualization of relevant constructs and terminology used to describe them. These issues hamper our ability to interpret study methods and findings, hinder efforts to integrate findings across studies to reach scientific consensus, and increase the likelihood of redundant efforts. We argue that multidisciplinary experts in this field require a universal language and clear, standardized terminology to further advance the important work of examining the effects of blast exposure on human health, performance, and well-being. To this end, we present a summary of descriptive conventions regarding the language scientists currently use when discussing blast-related exposures and outcomes based on findings from a recent scoping review. We then provide prescriptive conventions about how these terms should be used by clearly conceptualizing and explicitly defining relevant constructs. Specifically, we summarize essential concepts relevant to the study of blast, precisely distinguish between high-level blast and low-level blast, and discuss how the terms acute, chronic, exposure, and outcome should be used when referring to the health-related consequences of blast exposure.

White Matter Alteration Following SWAT Explosive Breaching Training and the Moderating Effect of a Neck Collar Device: A DTI and NODDI Study.

Special Weapons and Tactics (SWAT) personnel who practice breaching with blast exposure are at risk for blast-related head trauma. We aimed to investigate the impact of low-level blast exposure on underlying white matter (WM) microstructure based on diffusion tensor imaging (DTI) and neurite orientation and density imaging (NODDI) in SWAT personnel before and after breacher training. Diffusion tensor imaging is an advanced MRI technique sensitive to underlying WM alterations. NODDI is a novel MRI technique emerged recently that acquires diffusion weighted data from multiple shells modeling for different compartments in the microstructural environment in the brain. We also aimed to evaluate the effect of a jugular vein compression collar device in mitigating the alteration of the diffusion properties in the WM as well as its role as a moderator on the association between the diffusion property changes and the blast exposure. Twenty-one SWAT personnel (10 non-collar and 11 collar) completed the breacher training and underwent MRI at both baseline and after blast exposure. Diffusion weighted data were acquired with two shells (b = 1,000, 2,000 s/mm2) on 3T Phillips scanners. Diffusion tensor imaging metrices, including fractional anisotropy, mean, axial, and radial diffusivity, and NODDI metrics, including neurite density index (NDI), isotropic volume fraction (fiso), and orientation dispersion index, were calculated. Tract-based spatial statistics was used in the voxel-wise statistical analysis. Post hoc analyses were performed for the quantification of the pre- to post-blast exposure diffusion percentage change in the WM regions with significant group difference and for the assessment of the interaction of the relationship between blast exposure and diffusion alteration. The non-collar group exhibited significant pre- to post-blast increase in NDI (corrected P < .05) in the WM involving the right internal capsule, the right posterior corona radiation, the right posterior thalamic radiation, and the right sagittal stratum. A subset of these regions showed significantly greater alteration in NDI and fiso in the non-collar group when compared with those in the collar group (corrected P < .05). In addition, collar wearing exhibited a significant moderating effect for the alteration of fiso for its association with average peak pulse pressure. Our data provided initial evidence of the impact of blast exposure on WM diffusion alteration based on both DTI and NODDI. The mitigating effect of WM diffusivity changes and the moderating effect of collar wearing suggest that the device may serve as a promising solution to protect WM against blast exposure.

Evaluation of a Field-Ready Neurofunctional Assessment Tool for Use in a Military Environment.

The Office of Naval Research sponsored the Blast Load Assessment Sense and Test (BLAST) program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to provide a standardized approach to operationally relevant monitoring and analysis of service members exposed to single or repeated low-level blast. A critical piece of the BLAST team's solution was the development of the Brain Gauge technology which includes a cognitive assessment device that measures neurofunctional changes by testing sensory perceptions and a suite of mathematical algorithms that analyze the results of the test. The most recent versions of the technology are easily portable; the device is in the size and shape of a computer mouse. Tests can be administered in a matter of minutes and do not require oversight by a clinician, making Brain Gauge an excellent choice for field use. This paper describes the theoretical underpinnings and performance of a fieldable Brain Gauge technology for use with military populations. The methods used by the Brain Gauge have been documented in over 80 peer-reviewed publications. These papers are reviewed, and the utility of the Brain Gauge is described in terms of those publications. The Brain Gauge has been demonstrated to be an effective tool for assessing blast-induced neurotrauma and tracking its recovery. Additionally, the method parallels neurophysiological findings of animal models which provide insight into the sensitivity of specific metrics to mechanisms of information processing. The overall objective of the work was to provide an efficient tool, or tools, that can be effectively used for (1) determining stand-down criteria when critical levels of blast exposure have been reached and (2) tracking the brain health history until return-to-duty status is achieved. Neurofunctional outcome measures will provide the scientific link between blast sensors and the impact of blast on biological health. This calibration process is strengthened with outcome measures that have a biological basis that are paralleled in animal models. The integrative approach that utilizes the Brain Gauge technology will provide a significant advance for assessing the impact of blast exposure and support rapid, science-based decision-making that will ensure mission success and promote the protection of brain health in service members.

Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast

Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a neurodegenerative basis. Rats exposed to repetitive low-level blast exhibit chronic neurobehavioral traits and accumulate tau phosphorylated at threonine 181 (Thr181). Using data previously reported in separate studies we tested the hypothesis that region-specific patterns of Thr181 phosphorylation correlate with behavioral measures also previously determined and reported in the same animals. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization. There were no correlations with levels in amygdala or posterior neocortical regions. Particularly striking were asymmetrical effects on the right and left hippocampus. No systematic variation in head orientation toward the blast wave seems to explain the laterality. Levels did not correlate with behavioral measures of hyperarousal. Results were specific to Thr181 in that no correlations were observed for three other phospho-acceptor sites (threonine 231, serine 396, and serine 404). No consistent correlations were linked with total tau. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and the hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself. They also suggest an association linking blast injury with tauopathy, which has implications for understanding the relationship of chronic blast-related neurobehavioral syndromes in humans to neurodegenerative diseases.

Repeated Low-Level Blast Acutely Alters Brain Cytokines, Neurovascular Proteins, Mechanotransduction, and Neurodegenerative Markers in a Rat Model.

Exposure to the repeated low-level blast overpressure (BOP) periodically experienced by military personnel in operational and training environments can lead to deficits in behavior and cognition. While these low-intensity blasts do not cause overt changes acutely, repeated exposures may lead to cumulative effects in the brain that include acute inflammation, vascular disruption, and other molecular changes, which may eventually contribute to neurodegenerative processes. To identify these acute changes in the brain following repeated BOP, an advanced blast simulator was used to expose rats to 8.5 or 10 psi BOP once per day for 14 days. At 24 h after the final BOP, brain tissue was collected and analyzed for inflammatory markers, astrogliosis (GFAP), tight junction proteins (claudin-5 and occludin), and neurodegeneration-related proteins (Aβ40/42, pTau, TDP-43). After repeated exposure to 8.5 psi BOP, the change in cytokine profile was relatively modest compared to the changes observed following 10 psi BOP, which included a significant reduction in several inflammatory markers. Reduction in the tight junction protein occludin was observed in both groups when compared to controls, suggesting cerebrovascular disruption. While repeated exposure to 8.5 psi BOP led to a reduction in the Alzheimer’s disease (AD)-related proteins amyloid-β (Aβ)40 and Aβ42, these changes were not observed in the 10 psi group, which had a significant reduction in phosphorylated tau. Finally, repeated 10 psi BOP exposures led to an increase in GFAP, indicating alterations in astrocytes, and an increase in the mechanosensitive ion channel receptor protein, Piezo2, which may increase brain sensitivity to injury from pressure changes from BOP exposure. Overall, cumulative effects of repeated low-level BOP may increase the vulnerability to injury of the brain by disrupting neurovascular architecture, which may lead to downstream deleterious effects on behavior and cognition.

Neuropsychological, Neurocognitive, Vestibular, and Neuroimaging Correlates of Exposure to Repetitive Low-Level Blast Waves: Evidence From Four Nonoverlapping Samples of Canadian Breachers.

We assessed the utility of a battery of neuropsychological, neurocognitive, physiological (balance, ataxia, postural tremor), and neuroimaging measures for studying the effects of blast waves in breachers-a population repeatedly exposed to low-level blast during military training and operations. Data were collected from four nonoverlapping samples, in the course of similarly structured 4-day breacher training exercises in successive years involving a combination of indoor and outdoor blast events. In all cases, self-report and neuropsychological measures were administered once at baseline (i.e., 1 day before the start of training). In years 1-2, neurocognitive and physiological measures were administered daily before and after training. In years 3-4, neurocognitive data were collected once at baseline. In Year 4, we introduced 3 modifications to our design. First, in addition to breachers, we also collected data from sex-and age-matched military controls at the same time points. Second, we assessed balance, ataxia, and postural tremor immediately following blast exposure "in the field," enabling us to quantify its acute effects. Third, structural magnetic resonance imaging (MRI) scans were acquired before and after the 4-day training exercise to explore differences between breachers and controls at baseline, as well as possible training-related changes using voxel-based morphometry. These design modifications were made to enable us to test additional hypotheses in the context of the same training exercise. At baseline, scores on the "Rivermead Post Concussion Symptoms Questionnaire," "RAND SF-36" (physical functioning, role limitation due to physical health, social functioning, energy/fatigue, general health), and "Short Musculoskeletal Function Questionnaire" distinguished breachers from controls. Also at baseline, the MRI data revealed that there was greater regional gray matter volume in controls compared to breachers in the right superior frontal gyrus. Balance, ataxia, and postural tremor did not exhibit sensitivity to the acute effects of blast in the field, nor did neurocognitive measures to its cumulative or daily effects. Our exploratory results suggest that self-report neuropsychological measures and structural MRI hold promise as sensitive measures for quantifying the long-term, cumulative effects of blast exposure in breachers. We discuss the limitations of our study and the need for prospective longitudinal data for drawing causal inferences regarding the impact of blast exposure on breachers' health and performance.

Measurements of Infrasound Signatures From Grenade Blast During Training.

Military personnel during training and military operations are exposed to a large number of repeated exposures to low-level blast overpressure from a variety of sources. These exposures rarely produce a concussion, but anecdotal evidence from soldiers indicates that it can still cause transient neurological effects. Impulsive acoustic sources, such as the ones encountered during military training, are characterized by a broadband energy distribution with resulting pressure measurements that exhibit frequency components well within the infrasound range. This infrasound can couple directly with the human body and in this way alter or influence physiological processes up to inducing concussion-like symptoms. This study explores the presence of infrasound energy in measured acoustic signals collected during grenade training at Ft. Benning, GA. Acoustic data from traditional microphones and specialized infrasound microphones were collected during one training session and time and time-frequency analysis was performed to highlight the frequency content of the signals. The analysis of the collected measurements indicates peak SPLs between 140 and 160 dB during explosions corresponding to the shockwave. Also, high-intensity infrasound was observed during grenade explosions with significant energy in the infrasound range and in particular below 3 Hz. This energy appears in the form of three distinct tones at frequencies of 1.987, 2.296, and 2.528 Hz that are present only for the duration of the blast wave. The results presented in this article suggest that reported symptoms from military personnel exposed to repeated low-level blast may also be because of acoustic loading. Therefore, to take into account these findings, future studies aimed at characterizing the effects of repeated low-level blast exposure should consider including acoustic measurements in their investigations.