Association of Blast Exposure in Military Breaching with Intestinal Permeability Blood Biomarkers Associated with Leaky Gut.

Injuries and subclinical effects from exposure to blasts are of significant concern in military operational settings, including tactical training, and are associated with self-reported concussion-like symptomology and physiological changes such as increased intestinal permeability (IP), which was investigated in this study. Time-series gene expression and IP biomarker data were generated from "breachers" exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre-, post-, and follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and taking longer to think, dissipating ~16 h following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p = 0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n = 23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mild traumatic brain injury and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive functioning. These preliminary findings show for the first time within real-world military operational settings that exposures to blast can contribute to IP.

Fiscal Year 2018 National Defense Authorization Act, Section 734, Weapon Systems Line of Inquiry: Overview and Blast Overpressure Tool-A Module for Human Body Blast Wave Exposure for Safer Weapons Training.

INTRODUCTION: Experiences by service members in recent conflicts and training environments illuminate concerns about the possible effects of blast overpressure (BOP) exposure on brain health. Section 734 of the National Defense Authorization Act for Fiscal Year (FY) 2018 (Public Law 115-91) requires that the Secretary of Defense conducts a longitudinal medical study on blast pressure exposure of members of the Armed Forces during combat and training, and the Assistant Secretary of Defense for Health Affairs was assigned responsibility for fulfilling requirements. The study's goal is to improve DoD's understanding of the impact of BOP exposure from weapon systems on service members' brain health and inform policy for risk mitigation, unit readiness, and health care decisions. This article focuses on the activities of the Weapon Systems Line of Inquiry (LOI) and the development of a prototype BOP Tool. MATERIALS AND METHODS: The DoD established the Section 734 Workgroup, which developed a program structure with five LOIs. The Weapon Systems LOI coordinated, collated, and analyzed information on BOP resulting from heavy weapons and blast events to inform strategies, and accounted for emerging research on health effects and performance. Ongoing research was leveraged to develop a BOP Tool as a standalone module and for integration into the Range Managers Toolkit. RESULTS: The effort identified opportunities for the DoD to improve the clarity of communications about BOP exposure, risk, and safety; establish methods to leverage emerging research; and develop a prototype BOP Tool to predict exposure loads when firing heavy weapons in training. CONCLUSIONS: It is recommended that the DoD revises requirements and policy to improve and standardize safety guidance throughout research, development, testing, and evaluation; acquisition; and training. The validated BOP Tool allows users to generate a scenario to predict BOP exposure and allows service members to modify them during planning for safer training.

Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

Background and Objectives: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. Materials and Methods: After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. Results: We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. Conclusions: In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.

Investigation of the direct and indirect mechanisms of primary blast insult to the brain.

The interaction of explosion-induced blast waves with the head (i.e., a direct mechanism) or with the torso (i.e., an indirect mechanism) presumably causes traumatic brain injury. However, the understanding of the potential role of each mechanism in causing this injury is still limited. To address this knowledge gap, we characterized the changes in the brain tissue of rats resulting from the direct and indirect mechanisms at 24 h following blast exposure. To this end, we conducted separate blast-wave exposures on rats in a shock tube at an incident overpressure of 130 kPa, while using whole-body, head-only, and torso-only configurations to delineate each mechanism. Then, we performed histopathological (silver staining) and immunohistochemical (GFAP, Iba-1, and NeuN staining) analyses to evaluate brain-tissue changes resulting from each mechanism. Compared to controls, our results showed no significant changes in torso-only-exposed rats. In contrast, we observed significant changes in whole-body-exposed (GFAP and silver staining) and head-only-exposed rats (silver staining). In addition, our analyses showed that a head-only exposure causes changes similar to those observed for a whole-body exposure, provided the exposure conditions are similar. In conclusion, our results suggest that the direct mechanism is the major contributor to blast-induced changes in brain tissues.

Central and peripheral auditory abnormalities in chinchilla animal model of blast-injury.

Exposure to blast overpressure or high-intensity sound can cause injuries to the auditory system, which leads to hearing loss or tinnitus. In this study, we examined the involvement of peripheral auditory system (PAS), and central auditory system (CAS) changes after exposure to blast overpressure (15-25 psi) on Day 1 and additionally during 7 days of post blast time period in chinchillas. Auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and cochlear hair cell changes were measured or identified in post-blast period within 7 days to detect injuries in the PAS. In the CAS, changes in NMDAR1 (excitatory receptor) and GABAA (inhibitory receptor) as well as changes in serotonin (5-HT2A) and acetylcholine (AChR) receptors were examined in different brain regions: auditory cortex (AC), geniculate body (GB), inferior colliculus (IC) and amygdala by immunofluorescence staining. We observed the PAS abnormalities of increased ABR threshold and decreased DPOAE response in animals after blast exposure with hearing protection devices (e.g., earplug). Blast exposure also caused a reduction in both NMDAR1 and GABAA receptor levels in acute condition (post-blast or Day 1) in AC and IC, while serotonin and acetylcholine receptor levels displayed a biphasic response at Day 1 and Day 7 post-exposure. Results demonstrate that the earplug can protect the tympanic membrane and middle ear against structural damage, but the hearing level, cochlear outer hair cell, and the central auditory system (levels of excitatory and inhibitory neurotransmitter receptors) were only partially protected at the tested blast overpressure level. The findings in this study indicate that blast exposure can cause both peripheral and central auditory dysfunctions, and the central auditory response is independent of peripheral auditory damage. The CAS dysfunction is likely mediated by direct transmission of shockwaves in all the regions of central nervous system (CNS), including nerves and surrounding tissues along the auditory pathways. Hence, targeting central auditory neurotransmitter abnormalities may have a therapeutic benefit to attenuate blast-induced hearing loss and tinnitus.

Fast-Running Tools for Personalized Monitoring of Blast Exposure in Military Training and Operations.

INTRODUCTION: During training and combat operations, military personnel may be exposed to repetitive low-level blast while using explosives to gain entry or by firing heavy weapon systems such as recoilless weapons and high-caliber sniper rifles. This repeated exposure, even within allowable limits, has been associated with cognitive deficits similar to that of accidental and sports concussion such as delayed verbal memory, visual-spatial memory, and executive function. This article presents a novel framework for accurate calculation of the human body blast exposure in military heavy weapon training scenarios using data from the free-field and warfighter wearable pressure sensors. MATERIALS AND METHODS: The CoBi human body model generator tools were used to reconstruct multiple training scenes with different weapon systems. The CoBi Blast tools were used to develop the weapon signature and estimate blast overpressure exposure. The authors have used data from the free-field and wearable pressure sensors to evaluate the framework. RESULTS: Carl-Gustav and 0.50 caliber sniper training scenarios were used to demonstrate and validate the developed framework. These simulations can calculate spatially and temporally resolved blast loads on the whole human body and on specific organs vulnerable to blast loads, such as head, face, and lungs. CONCLUSIONS: This framework has numerous advantages including easier model setup and shorter simulation times. The framework is an important step towards developing an advanced field-applicable technology to monitor low-level blast exposure during heavy weapon military training and combat scenarios.

Variations in Constitutive Properties of the Fluid Elicit Divergent Vibrational and Pressure Response Under Shock Wave Loading.

We performed a characterization of the shock wave loading on the response of the specimen representing a simplified head model. A polycarbonate cylinder (2-in. outer diameter, wall thickness: 0.06 or 0.12 in.) was filled with two fluids: pure de-ionized water and 40% glycerol in water, which differ only slightly in their constitutive material properties. These two fluids were selected to represent the cerebrospinal fluid and cerebral blood, using their high strain rate viscosity as a primary selection criterion. The model specimen was exposed to a single shock wave with two nominal intensities: 70 and 130 kPa overpressure. The response of the model was measured using three strain gauges and three pressure sensors, one mounted on the front face of the cylinder and two embedded in the cylinder to measure the pressure inside of the fluid. We noted several discriminant characteristics in the collected data, which indicate that the type of fluid is strongly influencing the response. The vibrations of the cylinder walls are strongly correlated with the fluid kind. The similarity analysis via the Pearson coefficient indicated that the pressure waveforms in the fluid are only moderately correlated, and these results were further corroborated by Euclidean distance analysis. Continuous wavelet transform of pressure waveforms revealed that the frequency response is strongly correlated with the properties of the fluid. The observed differences in strain and pressure modalities stem from relatively small differences in the properties of the fluids used in this study.

Sensor orientation and other factors which increase the blast overpressure reporting errors.

This study compared the response of the wearable sensors tested against the industry-standard pressure transducers at blast overpressure (BOP) levels typically experienced in training. We systematically evaluated the effects of the sensor orientation with respect to the direction of the incident shock wave and demonstrated how the averaging methods affect the reported pressure values. The evaluated methods included averaging peak overpressure and impulse of all four sensors mounted on a helmet, taking the average of the three sensors, or isolating the incident pressure equivalent using two sensors. The experimental procedures were conducted in controlled laboratory conditions using the shock tube, and some of the findings were verified in field conditions with live fire charges during explosive breaching training. We used four different orientations (0°, 90°, 180°, and 270°) of the headform retrofitted with commonly fielded helmets (ACH, ECH, Ops-Core) with four B3 Blast Gauge sensors. We determined that averaging the peak overpressure values overestimates the actual dosage experienced by operators, which is caused by the reflected pressure contribution. This conclusion is valid despite the identified limitation of the B3 gauges that consistently underreport the peak reflected overpressure, compared to the industry-standard sensors. We also noted consistent overestimation of the impulse. These findings demonstrate that extreme caution should be exercised when interpreting occupational blast exposure results without knowing the orientation of the sensors. Pure numerical values without the geometrical, training-regime specific information such as the position of the sensors, the distance and orientation of the trainee to the source of the blast wave, and weapon system used will inevitably lead to erroneous estimation of the individual and cumulative blast overpressure (BOP) dosages. Considering that the 4 psi (~28 kPa) incident BOP is currently accepted as the threshold exposure safety value, a misinterpretation of exposure level may lead to an inaccurate estimation of BOP at the minimum standoff distance (MSD), or exclusion criteria.

The evolution of secondary flow phenomena and their effect on primary shock conditions in shock tubes: Experimentation and numerical model.

Compressed gas-driven shock tubes are widely used for laboratory simulation of primary blasts by accurately replicating pressure profiles measured in live-fire explosions. These investigations require sound characterization of the primary blast wave, including the temporal and spatial evolution of the static and dynamic components of the blast wave. The goal of this work is to characterize the propagation of shock waves in and around the exit of a shock tube via analysis of the primary shock flow, including shock wave propagation and decay of the shock front, and secondary flow phenomena. To this end, a nine-inch shock tube and a cylindrical sensing apparatus were used to determine incident and total pressures outside of the shock tube, highlighting the presence of additional flow phenomena. Blast overpressure, impulse, shock wave arrival times, positive phase duration, and shock wave planarity were examined using a finite element model of the system. The shock wave remained planar inside of the shock tube and lost its planarity upon exiting. The peak overpressure and pressure impulse decayed rapidly upon exit from the shock tube, reducing by 92-95%. The primary flow phenomenon, or the planar shock front, is observed within the shock tube, while two distinct flow phenomena are a result of the shock wave exiting the confines of the shock tube. A vortex ring is formed as the shock wave exited the shock tube into the still, ambient air, which induces a large increase in the total pressure impulse. Additionally, a rarefaction wave was formed following shock front expansion, which traveled upstream into the shock tube, reducing the total and incident pressure impulses for approximately half of the simulated region.

Does Blast Exposure to the Torso Cause a Blood Surge to the Brain?

The interaction of explosion-induced blast waves with the torso is suspected to contribute to brain injury. In this indirect mechanism, the wave-torso interaction is assumed to generate a blood surge, which ultimately reaches and damages the brain. However, this hypothesis has not been comprehensively and systematically investigated, and the potential role, if any, of the indirect mechanism in causing brain injury remains unclear. In this interdisciplinary study, we performed experiments and developed mathematical models to address this knowledge gap. First, we conducted blast-wave exposures of Sprague-Dawley rats in a shock tube at incident overpressures of 70 and 130 kPa, where we measured carotid-artery and brain pressures while limiting exposure to the torso. Then, we developed three-dimensional (3-D) fluid-structure interaction (FSI) models of the neck and cerebral vasculature and, using the measured carotid-artery pressures, performed simulations to predict mass flow rates and wall shear stresses in the cerebral vasculature. Finally, we developed a 3-D finite element (FE) model of the brain and used the FSI-computed vasculature pressures to drive the FE model to quantify the blast-exposure effects in the brain tissue. The measurements from the torso-only exposure experiments revealed marginal increases in the peak carotid-artery overpressures (from 13.1 to 28.9 kPa). Yet, relative to the blast-free, normotensive condition, the FSI simulations for the blast exposures predicted increases in the peak mass flow rate of up to 255% at the base of the brain and increases in the wall shear stress of up to 289% on the cerebral vasculature. In contrast, our simulations suggest that the effect of the indirect mechanism on the brain-tissue-strain response is negligible (<1%). In summary, our analyses show that the indirect mechanism causes a sudden and abundant stream of blood to rapidly propagate from the torso through the neck to the cerebral vasculature. This blood surge causes a considerable increase in the wall shear stresses in the brain vasculature network, which may lead to functional and structural effects on the cerebral veins and arteries, ultimately leading to vascular pathology. In contrast, our findings do not support the notion of strain-induced brain-tissue damage due to the indirect mechanism.

A Comprehensive Review of Experimental Rodent Models of Repeated Blast TBI.

We reviewed the relevant literature delineating advances in the development of the experimental models of repeated blast TBI (rbTBI). It appears this subject is a relatively unexplored area considering the first work published in 2007 and the bulk of peer-reviewed papers was published post-2011. There are merely 34 papers published to date utilizing rodent rbTBI models. We performed an analysis and extracted basic parameters to capture the characteristics of the exposure conditions (the blast intensity, inter-exposure interval and the number of exposures), the age and weight of the animal models most commonly used in the studies, and their endpoints. Our analysis revealed three strains of rodents are predominantly used: Sprague Dawley and Long Evans rats and wild type (C57BL/6J) mice, and young adult animals 8 to 12-week-old are a preferred choice. Typical exposure conditions are the following: (1) peak overpressure in the 27-145 kPa (4-21 psi) range, (2) number of exposures: 2 (13.9%), 3 (63.9%), 5 (16.7%), or 12 (5.6%) with a single exposure used for a baseline comparison in 41.24% of the studies. Two inter-exposure interval durations were used: (1) short (1-30 min.) and (2) extended (24 h) between consecutive shock wave exposures. The experiments included characterization of repeated blast exposure effects on auditory, ocular and neurological function, with a focus on brain etiology in most of the published work. We present an overview of major histopathological findings, which are supplemented by studies implementing MRI (DTI) and behavioral changes after rbTBI in the acute (1-7 days post-injury), subacute (7-14 days), and chronic (>14 days) phases post-injury.

Occupational Blast Wave Exposure During Multiday 0.50 Caliber Rifle Course.

Research on blast overpressure (BOP) experienced by military personnel in operations like breaching, identifies transient, measurable effects on operator readiness. Specifically, blast seems to be associated with suppressed response speed and cognitive function. This work evaluates 50 caliber weapon systems to ascertain BOP effects from the weapon usage. Marksmen were a collection of professionals who use 0.50 caliber weapon systems as part of their daily activities, and the environment measured was during a training course. The 20 human subjects were equipped with B3 blast gauges and occupational BOP exposure monitored over the course of 3 day training period with measurements taken from 500+ shots. We noted a considerable variation in total cumulative peak pressure (50-350 psi) and impulse (25-180 psi·ms) values. The frequency analysis (number of shots fired by the trainee) revealed that the number of exposures per day varied between 4 and 27 per day (peak at 7: 14.3% of the data), and 2 to 17 per hour (peak at 8: 18% of the data). The cumulative number of exposures was 24-50 per trainee. The neurocognitive performance was evaluated using Defense Automated Neurobehavioral Assessment (DANA) Rapid: Simple Reaction Time (SRT), Procedural Reaction Time (PRT) and Go/No-Go (GNG). The results recorded before the training were a baseline for each training day and compared with the results recorded after and at the end of the day. Only PRT and GNG tests revealed a cumulative increase in proportion of subjects with slowed reaction times over the progression of course with concomitant dispersion increase at the end of the day. Noticeably, on average 2/3rd of the trainees performed faster, while 1/3rd of trainees performed these tasks slower, but there was no correlation with the cumulative pressure dosage. The fatigue appears as an aggravating factor affecting the neurocognitive performance, and a more sophisticated evaluation regimen is necessary to discern potential neurological effects. Additional investigation is needed to understand the increasing dispersion of results between subjects and future works should be mindful of such continued trends. Future work should seek to determine the recovery period and longitudinal effects of heavy usage of these weapon systems.

Characterization of a controlled shock wave delivered by a pneumatic table-top gas driven shock tube.

Blast simulators facilitate the creation of shock waves and measurement of pressure morphology in a controlled laboratory setting and are currently a vital model for replicating blast-induced neurotrauma. Due to the maintenance and operation cost of conventional blast simulators, we developed a pneumatic, table-top, gas-driven shock tube to test an alternative method of shock wave generation using a membrane-less driver section. Its unique operational mechanism based on air gun technology does not rely on a plastic membrane rupture for the generation of pressure pulses, allowing the simulator to be quickly reset and thus decreasing the experimental turnaround time. The focus of this study is to demonstrate that this proof-of-concept device can generate shock waves with diverse characteristics based on the selection of driver gas, driver pressurization, and driven section material. Pressure waves were generated using compressed nitrogen or helium at 15 psig and 80 psig and were analyzed based on their velocity and profile shape characteristics. At 15 psig, independent of the type of driver gas, driver pressurization, and driven section material, pressure pulses travelled at sonic velocities. At 80 psig, generation of shock waves was observed in all conditions. The choice of the driver gas affected the velocities of the resulting pressure waves and the shape of pressure waveforms, particularly the peak overpressure and rise time values. Our results demonstrate that depending on the selection of driver gas and magnitude of driver pressurization, the shock wave signatures can be controlled and altered using a piston-based driver section.

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model.

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

Effect of Tissue Material Properties in Blast Loading: Coupled Experimentation and Finite Element Simulation.

Computational models of blast-induced traumatic brain injury (bTBI) require a robust definition of the material models of the brain. The mechanical constitutive models of these tissues are difficult to characterize, leading to a wide range of values reported in literature. Therefore, the sensitivity of the intracranial pressure (ICP) and maximum principal strain to variations in the material model of the brain was investigated through a combined computational and experimental approach. A finite element model of a rat was created to simulate a shock wave exposure, guided by the experimental measurements of rats subjected to shock loading conditions corresponding to that of mild traumatic brain injury in a field-validated shock tube. In the numerical model, the properties of the brain were parametrically varied. A comparison of the ICP measured at two locations revealed that experimental and simulated ICP were higher in the cerebellum (p < 0.0001), highlighting the significance of pressure sensor locations within the cranium. The ICP and strain were correlated with the long-term bulk (p < 0.0001) and shear moduli (p < 0.0001), with an 80 MPa effective bulk modulus value matching best with experimental measurements. In bTBI, the solution is sensitive to the brain material model, necessitating robust validation methods.

Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury.

Understanding the mechanisms underlying traumatic neural injury and the sequelae of events in the acute phase is important for deciding on the best window of therapeutic intervention. We hypothesized that evoked potentials (EP) recorded from the cerebellar cortex can detect mild levels of neural trauma and provide a qualitative assessment tool for progression of cerebellar injury in time. The cerebellar local field potentials evoked by a mechanical tap on the hand and collected with chronically implanted micro-ECoG arrays on the rat cerebellar cortex demonstrated substantial changes both in amplitude and timing as a result of blast-wave induced injury. The results revealed that the largest EP changes occurred within the first day of injury, and partial recoveries were observed from day-1 to day-3, followed by a period of gradual improvements (day-7 to day-14). The mossy fiber (MF) and climbing fiber (CF) mediated components of the EPs were affected differentially. The behavioral tests (ladder rung walking) and immunohistological analysis (calbindin and caspase-3) did not reveal any detectable changes at these blast pressures that are typically considered as mild (100-130 kPa). The results demonstrate the sensitivity of the electrophysiological method and its use as a tool to monitor the progression of cerebellar injuries in longitudinal animal studies.

Effective testing of personal protective equipment in blast loading conditions in shock tube: Comparison of three different testing locations.

We exposed a headform instrumented with 10 pressure sensors mounted flush with the surface to a shock wave with three nominal intensities: 70, 140 and 210 kPa. The headform was mounted on a Hybrid III neck, in a rigid configuration to eliminate motion and associated pressure variations. We evaluated the effect of the test location by placing the headform inside, at the end and outside of the shock tube. The shock wave intensity gradually decreases the further it travels in the shock tube and the end effect degrades shock wave characteristics, which makes comparison of the results obtained at three locations a difficult task. To resolve these issues, we developed a simple strategy of data reduction: the respective pressure parameters recorded by headform sensors were divided by their equivalents associated with the incident shock wave. As a result, we obtained a comprehensive set of non-dimensional parameters. These non-dimensional parameters (or amplification factors) allow for direct comparison of pressure waveform characteristic parameters generated by a range of incident shock waves differing in intensity and for the headform located in different locations. Using this approach, we found a correlation function which allows prediction of the peak pressure on the headform that depends only on the peak pressure of the incident shock wave (for specific sensor location on the headform), and itis independent on the headform location. We also found a similar relationship for the rise time. However, for the duration and impulse, comparable correlation functions do not exist. These findings using a headform with simplified geometry are baseline values and address a need for the development of standardized parameters for the evaluation of personal protective equipment (PPE) under shock wave loading.

A Single Primary Blast-Induced Traumatic Brain Injury in a Rodent Model Causes Cell-Type Dependent Increase in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Isoforms in Vulnerable Brain Regions.

Blast-induced traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and in training sites with long-term neurological and psychological pathologies. Previous studies from our laboratory demonstrated activation of oxidative stress pathways after blast injury, but their distribution among different brain regions and their impact on the pathogenesis of bTBI have not been explored. The present study examined the protein expression of two isoforms: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 (NOX1, NOX2), corresponding superoxide production, a downstream event of NOX activation, and the extent of lipid peroxidation adducts of 4-hydroxynonenal (4HNE) to a range of proteins. Brain injury was evaluated 4 h after the shock-wave exposure, and immunofluorescence signal quantification was performed in different brain regions. Expression of NOX isoforms displayed a differential increase in various brain regions: in hippocampus and thalamus, there was the highest increase of NOX1, whereas in the frontal cortex, there was the highest increase of NOX2 expression. Cell-specific analysis of changes in NOX expression with respect to corresponding controls revealed that blast resulted in a higher increase of NOX1 and NOX 2 levels in neurons compared with astrocytes and microglia. Blast exposure also resulted in increased superoxide levels in different brain regions, and such changes were reflected in 4HNE protein adduct formation. Collectively, this study demonstrates that primary blast TBI induces upregulation of NADPH oxidase isoforms in different regions of the brain parenchyma and that neurons appear to be at higher risk for oxidative damage compared with other neural cells.

On the Accurate Determination of Shock Wave Time-Pressure Profile in the Experimental Models of Blast-Induced Neurotrauma.

Measurement issues leading to the acquisition of artifact-free shock wave pressure-time profiles are discussed. We address the importance of in-house sensor calibration and data acquisition sampling rate. Sensor calibration takes into account possible differences between calibration methodology in a manufacturing facility, and those used in the specific laboratory. We found in-house calibration factors of brand new sensors differ by less than 10% from their manufacturer supplied data. Larger differences were noticeable for sensors that have been used for hundreds of experiments and were as high as 30% for sensors close to the end of their useful lifetime. These observations were despite the fact that typical overpressures in our experiments do not exceed 50 psi for sensors that are rated at 1,000 psi maximum pressure. We demonstrate that sampling rate of 1,000 kHz is necessary to capture the correct rise time values, but there were no statistically significant differences between peak overpressure and impulse values for low-intensity shock waves (Mach number <2) at lower rates. We discuss two sources of experimental errors originating from mechanical vibration and electromagnetic interference on the quality of a waveform recorded using state-of-the-art high-frequency pressure sensors. The implementation of preventive measures, pressure acquisition artifacts, and data interpretation with examples, are provided in this paper that will help the community at large to avoid these mistakes. In order to facilitate inter-laboratory data comparison, common reporting standards should be developed by the blast TBI research community. We noticed the majority of published literature on the subject limits reporting to peak overpressure; with much less attention directed toward other important parameters, i.e., duration, impulse, and dynamic pressure. These parameters should be included as a mandatory requirement in publications so the results can be properly compared with others.

Tailoring the Blast Exposure Conditions in the Shock Tube for Generating Pure, Primary Shock Waves: The End Plate Facilitates Elimination of Secondary Loading of the Specimen.

The end plate mounted at the mouth of the shock tube is a versatile and effective implement to control and mitigate the end effects. We have performed a series of measurements of incident shock wave velocities and overpressures followed by quantification of impulse values (integral of pressure in time domain) for four different end plate configurations (0.625, 2, 4 inches, and an open end). Shock wave characteristics were monitored by high response rate pressure sensors allocated in six positions along the length of 6 meters long 229 mm square cross section shock tube. Tests were performed at three shock wave intensities, which was controlled by varying the Mylar membrane thickness (0.02, 0.04 and 0.06 inch). The end reflector plate installed at the exit of the shock tube allows precise control over the intensity of reflected waves penetrating into the shock tube. At the optimized distance of the tube to end plate gap the secondary waves were entirely eliminated from the test section, which was confirmed by pressure sensor at T4 location. This is pronounced finding for implementation of pure primary blast wave animal model. These data also suggest only deep in the shock tube experimental conditions allow exposure to a single shock wave free of artifacts. Our results provide detailed insight into spatiotemporal dynamics of shock waves with Friedlander waveform generated using helium as a driver gas and propagating in the air inside medium sized tube. Diffusion of driver gas (helium) inside the shock tube was responsible for velocity increase of reflected shock waves. Numerical simulations combined with experimental data suggest the shock wave attenuation mechanism is simply the expansion of the internal pressure. In the absence of any other postulated shock wave decay mechanisms, which were not implemented in the model the agreement between theory and experimental data is excellent.