Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts.

Repeated blast-traumatic brain injury (blast-TBI) has been hypothesized to cause persistent and unusual neurological and psychiatric symptoms in service members returning from war zones. Blast-wave primary effects have been supposed to induce damage and molecular alterations in the brain. However, the mechanisms through which the primary effect of an explosive-driven blast wave generate brain lesions and induce brain consequences are incompletely known. Prior findings from rat brains exposed to two consecutive explosive-driven blasts showed molecular changes (hyperphosphorylated-Tau, AQP4, S100ß, PDGF, and DNA-polymerase-ß) that varied in magnitude and direction across different brain regions. We aimed to compare, in an unbiased manner, the proteomic profile in the hippocampus of double blast vs sham rats using mass spectrometry (MS). Data showed differences in up- and down-regulation for protein abundances in the hippocampus of double blast vs sham rats. Tandem mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before in blast studies, such as increases in MAGI3, a scaffolding protein at cell-cell junctions, which were confirmed by Western blotting analyses. Due to the absence of behavioral and obvious histopathological changes as described in our previous publications, these proteomic data further support the existence of an asymptomatic blast-induced molecular altered status (ABIMAS) associated with specific protein changes in the hippocampus of rats repeatedly expsosed to blast waves generated by explosive-driven detonations.

Neuroinflammation Profiling of Brain Cytokines Following Repeated Blast Exposure.

Due to use of explosive devices and heavy weapons systems in modern conflicts, the effect of BW on the brain and body is of increasing concern. These exposures have been commonly linked with neurodegenerative diseases and psychiatric disorders in veteran populations. A likely neurobiological link between exposure to blasts and the development of neurobehavioral disorders, such as depression and PTSD, could be neuroinflammation triggered by the blast wave. In this study, we exposed rats to single or repeated BW (up to four exposures-one per day) at varied intensities (13, 16, and 19 psi) to mimic the types of blast exposures that service members may experience in training and combat. We then measured a panel of neuroinflammatory markers in the brain tissue with a multiplex cytokine/chemokine assay to understand the pathophysiological process(es) associated with single and repeated blast exposures. We found that single and repeated blast exposures promoted neuroinflammatory changes in the brain that are similar to those characterized in several neurological disorders; these effects were most robust after 13 and 16 psi single and repeated blast exposures, and they exceeded those recorded after 19 psi repeated blast exposures. Tumor necrosis factor-alpha and IL-10 were changed by 13 and 16 psi single and repeated blast exposures. In conclusion, based upon the growing prominence of negative psychological health outcomes in veterans and soldiers with a history of blast exposures, identifying the molecular etiology of these disorders, such as blast-induced neuroinflammation, is necessary for rationally establishing countermeasures and treatment regimens.

Double Blast Wave Primary Effect on Synaptic, Glymphatic, Myelin, Neuronal and Neurovascular Markers.

Explosive blasts are associated with neurological consequences as a result of blast waves impact on the brain. Yet, the neuropathologic and molecular consequences due to blast waves vs. blunt-TBI are not fully understood. An explosive-driven blast-generating system was used to reproduce blast wave exposure and examine pathological and molecular changes generated by primary wave effects of blast exposure. We assessed if pre- and post-synaptic (synaptophysin, PSD-95, spinophilin, GAP-43), neuronal (NF-L), glymphatic (LYVE1, podoplanin), myelin (MBP), neurovascular (AQP4, S100ß, PDGF) and genomic (DNA polymerase-ß, RNA polymerase II) markers could be altered across different brain regions of double blast vs. sham animals. Twelve male rats exposed to two consecutive blasts were compared to 12 control/sham rats. Western blot, ELISA, and immunofluorescence analyses were performed across the frontal cortex, hippocampus, cerebellum, and brainstem. The results showed altered levels of AQP4, S100ß, DNA-polymerase-ß, PDGF, synaptophysin and PSD-95 in double blast vs. sham animals in most of the examined regions. These data indicate that blast-generated changes are preferentially associated with neurovascular, glymphatic, and DNA repair markers, especially in the brainstem. Moreover, these changes were not accompanied by behavioral changes and corroborate the hypothesis for which an asymptomatic altered status is caused by repeated blast exposures.

Study on the mesh size determination method of blast wave numerical simulation with strong applicability.

With the rapid development of computer hardware and software technology, numerical simulations have become one of the most important tools for studying propagation law of blast wave. Results of numerical simulations of explosion events greatly depend on the mesh size. The mesh size determination methods in the literature are relatively weak in generality. In this paper, a mesh size determination method with strong applicability is proposed. According to this method, the mesh size is the product of the scale coefficient and the third root of the equivalent TNT mass. The scale coefficient is related to the model dimension, scaled distance and simulation accuracy, and is independent of the TNT shape and the location of the detonation point. A large number of numerical simulation results confirm the accuracy of this method. The recommended scale coefficient to meet the engineering accuracy requirements is related to the model dimension and scaled distance. In general, when the scaled distance and model dimension are larger, the recommended scale coefficient will be larger. In this paper, the figures and tables of the recommended scale coefficients of 1D, 2D and 3D models varying with the scaled distance are given, and their rationality is verified by the existing numerical simulation events of blast wave. They can be used as a reference to determine the mesh size in numerical simulation of blast wave.

Study on chest injury and bulletproof vest protection under the combined action of blast wave and fragments.

Using a simulation based method, this paper analysis the damage effect of blast wave and fragments on human body and the protective effect of bulletproof vest. The results show that compared with the single blast shock wave, the chest injury is more serious under the combined action of blast shock wave and fragments. The peak stress of sternum, costal cartilage and rib increases by 334.34%, 170.23% and 39.72%, respectively. The peak stress on the side of the lung decreases by 3.95%, with little change. The peak stress on the front and back of the lung increases by 83.58% and 409.09% respectively. Overall, the lung injury is aggravated. With the addition of the bulletproof vest, the damage caused by fragments is reduced, and the peak stress of the sternum and the costal cartilage decreases by 48.77% and 69.78%, respectively. Due to the interaction of the blast wave with the vest and the chest, the damage caused by blast wave is aggravated. The peak stress of rib increases by 13.55%, and the peak stress of lung front, side and back increases by 1.22%, 6.51% and 3.57%, respectively.

Transient Response of Miniature Piezoresistive Pressure Sensor Dedicated to Blast Wave Monitoring.

Blast waves generated by energetic materials involve very fast time variations in the pressure. One important issue for blast wave metrology is the accurate measurement (typical precision in the range of ±5% or better) of the static overpressure peak. For most near field configurations, this measurement requires ultra-fast sensors with response times lower than a few microseconds. In this paper, we design, model, fabricate and characterize a new ultra-fast sensor using piezo-resistive gauges at the center of a miniaturized and rectangular silicon membrane. When a pressure step of 10 bar is applied to the membrane, the signal delivered to the sensor output presents dampened oscillations, with a resonant frequency of 20.6 MHz and quality factor of 24,700 ns after the arrival of the shock wave. After removing undesirable drifts that appear after 700 ns, we may expect the sensor to have a response time (at ±5%) of 1.2 µs. Consequently, the proposed pressure sensor could be advantageously used for the accurate measurement of static overpressure peaks in blast wave experiments.

Effect of driver gas composition on production of scaled Friedlander waveforms in an open-ended shock tube model.

With the evolution of modern warfare and the increased use of improvised explosive devices (IEDs), there has been an increase in blast-induced traumatic brain injuries (bTBI) among military personnel and civilians. The increased prevalence of bTBI necessitates bTBI models that result in a properly scaled injury for the model organism being used. The primary laboratory model for bTBI is the shock tube, wherein a compressed gas ruptures a thin membrane, generating a shockwave. To generate a shock wave that is properly scaled from human to rodent subjects many pre-clinical models strive for a short duration and high peak overpressure while fitting a Friedlander waveform, the ideal representation of a blast wave. A large variety of factors have been experimentally characterized in attempts to create an ideal waveform, however we found current research on the gas composition being used to drive shock wave formation to be lacking. To better understand the effect the driver gas has on the waveform being produced, we utilized a previously established murine shock tube bTBI model in conjunction with several distinct driver gasses. In agreement with previous findings, helium produced a shock wave most closely fitting the Friedlander waveform in contrast to the plateau-like waveforms produced by some other gases. The peak static pressure at the exit of the shock tube and total pressure 5 cm from the exit have a strong negative correlation with the density of the gas being used: helium the least dense gas used produces the highest peak overpressure. Density of the driver gas also exerts a strong positive effect on the duration of the shock wave, with helium producing the shortest duration wave. Due to its ability to produce a Friedlander waveform and produce a waveform following proper injury scaling guidelines, helium is an ideal gas for use in shock tube models for bTBI.

Revealing the Effect of Skull Deformation on Intracranial Pressure Variation During the Direct Interaction Between Blast Wave and Surrogate Head.

Intracranial pressure (ICP) during the interaction between blast wave and the head is a crucial evaluation criterion for blast-induced traumatic brain injury (bTBI). ICP variation is mainly induced by the blast wave transmission and skull deformation. However, how the skull deformation influences the ICP remains unclear, which is meaningful for mitigating bTBI. In this study, both experimental and numerical models are developed to elucidate the effect of skull deformation on ICP variation. Firstly, we performed the shock tube experiment of the high-fidelity surrogate head to measure the ICP, the blast overpressure, and the skull surface strain of specific positions. The results show that the ICP profiles of all measured points show oscillations with positive and negative change, and the variation is consistent with the skull surface strain. Further numerical analysis reveals that when the blast wave reaches the measured point, the peak overpressure transmits directly through the skull to the brain, forming the local positive ICP peak, and the impulse induces the local inward deformation of the skull. As the peak overpressure passes through, the blast impulse impacts the nearby skull supported by the soft and incompressible brain tissue and extrudes the skull outward in the initial position. The inward and outward skull deformation leads to the oscillation of ICP. These numerical analyses agree with experimental results, which explain the appearance of negative and positive ICP peaks and the synchronization of negative ICP with surface strain. The study has implications for medical injury diagnosis and protective equipment design.

Frequency Bandwidth of Pressure Sensors Dedicated to Blast Experiments.

New broadband (>1 MHz) pressure sensors are regularly reported in the literature to measure the overpressure of blast waves. However, the frequency bandwidth needed to accurately measure such overpressure has not yet been clearly discussed. In this article, we present a methodology to determine the bandwidth required to estimate the overpressure magnitude at the front of a blast wave, in order to obtain a desired estimation accuracy. The bandwidth is derived here by using Kingery and Bulmash data.

Blast Waves Cause Immune System Dysfunction and Transient Bone Marrow Failure in a Mouse Model.

Explosive devices, either conventional or improvised, are common sources of injuries during combat, civil unrest, and terror attacks, resulting in trauma from exposure to blast. A blast wave (BW), a near-instantaneous rise in pressure followed by a negative pressure, propagates through the body in milliseconds and can affect physiology for days/months after exposure. Epidemiological data show that blast-related casualties result in significantly higher susceptibility to wound infections, suggesting long-lasting immune modulatory effects from blast exposure. The mechanisms involved in BW-induced immune changes are poorly understood. We evaluated the effects of BW on the immune system using an established murine model. Animals were exposed to BWs (using an Advanced Blast Simulator), followed by longitudinally sampling for 14 days. Blood, bone marrow, and spleen were analyzed for changes in the 1) complete blood count (CBC), and 2) composition of bone marrow cells (BMC) and splenocytes, and 3) concentrations of systemic cytokines/chemokines. Our data demonstrate that BW results in transient bone marrow failure and long-term changes in the frequency and profile of progenitor cell populations. Viability progressively decreased in hematopoietic stem cells and pluripotent progenitor cells. Significant decrease of CD4+ T cells in the spleen indicates reduced functionality of adaptive immune system. Dynamic changes in the concentrations of several cytokines and chemokines such as IL-1α and IL-17 occurred potentially contributing to dysregulation of immune response after trauma. This work lays the foundation for identifying the potential mechanisms behind BW's immunosuppressive effects to inform the recognition of this compromised status is crucial for the development of therapeutic interventions for infections to reduce recovery time of wounded patients injured by explosive devices.

Theft-Safe Explosive Mixtures Based on Hydrogen Peroxide: Study of Properties and Built-In Self-Deactivation Kinetics.

The current focus on both environmental and general safety is an important issue in the field of explosives. As such, environmentally-friendly explosives, based on hydrogen peroxide (HTP) as an oxidising agent, are of significant interest. These explosives can be designed to undergo self-deactivation, denying access to them by any unlawful third parties that may attempt scavenging blasting sites for any residual energetic materials. Such deactivation also improves blasting safety, as, after a set time, misfired charges no longer pose any explosive threat. In this work, we have designed HTP-based explosive formulations that undergo deactivation after approximately 12 h. To this effect, Al powders were used both as fuels and HTP decomposition promoters. The shock wave parameters and ability to perform mechanical work of the proposed explosive formulations are comparable to those of dynamites and bulk emulsion explosives, and the details of the changes of these parameters over time are also reported.

Analyzing Transverse Momentum Spectra of Pions, Kaons and Protons in p-p, p-A and A-A Collisions via the Blast-Wave Model with Fluctuations.

The transverse momentum spectra of different types of particles, π±, K±, p and p¯, produced at mid-(pseudo)rapidity in different centrality lead-lead (Pb-Pb) collisions at 2.76 TeV; proton-lead (p-Pb) collisions at 5.02 TeV; xenon-xenon (Xe-Xe) collisions at 5.44 TeV; and proton-proton (p-p) collisions at 0.9, 2.76, 5.02, 7 and 13 TeV, were analyzed by the blast-wave model with fluctuations. With the experimental data measured by the ALICE and CMS Collaborations at the Large Hadron Collider (LHC), the kinetic freeze-out temperature, transverse flow velocity and proper time were extracted from fitting the transverse momentum spectra. In nucleus-nucleus (A-A) and proton-nucleus (p-A) collisions, the three parameters decrease with the decrease of event centrality from central to peripheral, indicating higher degrees of excitation, quicker expansion velocities and longer evolution times for central collisions. In p-p collisions, the kinetic freeze-out temperature is nearly invariant with the increase of energy, though the transverse flow velocity and proper time increase slightly, in the considered energy range.

Mild blast wave exposure produces intensity-dependent changes in MMP2 expression patches in rat brains - Findings from different blast severities.

Matrix metalloproteinase 2 (MMP2) is a gelatinase with multiple functions at the neurovascular interface, including local modification of the glia limitans to facilitate access of immune cells into the brain and amyloid-beta degradation during responses to injury or disease. This study examines regional changes in immunoreactive MMP2 in the rat brain after a single mild (2.7-7.9 psi peak) or moderate (13-17.5 psi peak) blast overpressure (BOP) exposure. Immunopositive MMP2 expression was examined quantitatively in histological sections of decalcified rat heads as a marker at 2, 24, and 72 h after BOP. The MMP2 immunoreactivity was isolated to patchy deposits in brain parenchyma surrounding blood vessels. Separate analyses were conducted for the cerebellum, brain stem caudal to the thalamo-mesencephalic junction, and the cerebrum (including diencephalon). The deposits varied in number, size, staining homogeneity (standard deviation of immunopositive region), and a cumulative measure, the product of size, average intensity and number, as a function of blast intensity and time. The sequences of changes in MMP2 spots from sham control animals suggested that the mild BOP exposure differences normalized within 72 h. However, the responses to moderate exposure revealed a delayed response at 72 h in the subtentorial brain stem and the cerebrum, but not the cerebellum. Hence, local MMP2 responses may be a contextual biomarker for locally regulated responses to widely distributed brain injury foci.

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 (Aß40/42, 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-ß (Aß)40 and Aß42, 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.

Static and Dynamic Performances of Chopped Carbon-Fiber-Reinforced Mortar and Concrete Incorporated with Disparate Lengths.

The impact load, such as seismic and shock wave, sometimes causes severe damage to the reinforced concrete structures. This study utilized different lengths of chopped carbon fibers to develop a carbon-fiber-reinforced mortar (CFRM) and carbon-fiber-reinforced concrete (CFRC) with high impact and anti-shockwave resistance. The different lengths (6, 12, and 24 mm) of chopped carbon fibers were pneumatically dispersed and uniformly mixed into the cement with a 1% weight proportion. Then the CFRM and CFRC specimens were made for static and dynamic tests. The compressive and flexural strengths of the specimens were determined by using the standard ASTM C39/C 39M and ASTM C 293-02, respectively. Meanwhile, a free-fall impact test was done according to ACI 544.2R-89, which was used to test the impact resistances of the specimens under different impact energies. The CFRM and CFRC with a length of 6 mm exhibit maximum compressive strength. Both flexural and free-fall impact test results show that the 24 mm CFRM and CFRC enhances their maximum flexural strength and impact numbers more than the other lengths of CFRM, CFRC, and the benchmark specimens. After impact tests, the failure specimens were observed in a high-resolution optical microscope, to identify whether the failure mode is slippage or rupture of the carbon fiber. Finally, a blast wave explosion test was conducted to verify that the blast wave resistance of the 24 mm CFRC specimen was better than the 12 mm CFRC and benchmark specimens.

Helmet chinstrap protective role in maxillofacial blast injury.

BACKGROUND: The protective role of helmet accessories in moderating stress load generated by explosion shock waves of explosive devices is usually neglected. OBJECTIVE: In the presented study, the protective role of the helmet chinstrap against the impulse and overpressure experienced by the maxillofacial region were examined. METHODS: The explosion shock wave and skull interaction were investigated under three different configurations: (1) unprotected skull, (2) skull with helmet (3) skull with helmet and chinstrap. For this purpose, a 3D finite element model (FEM) was constructed to mimic the investigated biomechanics module. Three working conditions were set according to different explosive charges and distances to represent different load conditions. Case 1: 500 mg explosive trinitrotoluene (TNT), 3 cm, case 2: 1000 mg TNT, 3 cm, and case 3: 1000 mg TNT and 6 cm distance to the studied object. The explosion effect was discussed by examining the shock wave stress flow pattern. Three points were selected on the skull and the stress curve of each point position were illustrated for each case study. RESULTS: The results showed that the helmet chinstrap can reduce the explosive injuries and plays a protective role in the maxillofacial region, especially for the mandible.

Caravan explosions: a case series of burns patients at the Royal Brisbane and Women's Hospital.

BACKGROUND: Caravan explosions due to gas cylinder explosions or gas leaks are responsible for a small but significantly injured group of burns patients. Those involved in explosions are sometimes assumed to be at risk of primary blast wave injury; however, the likelihood of such injuries is unclear. The aim of this research was to seek evidence of primary blast injury in groups defined by clinicians as having sustained burns in explosive and non-explosive events. METHODS: This is a single-centre case series of patients with caravan-related burns from 2009 to 2019, identified using the burns data registry at the Royal Brisbane and Women's Hospital. Patients were divided into two groups based on the mechanism of injury, with injuries sustained from either a gas bottle explosion (group 1) or from gas ignition (group 2). RESULTS: Twenty-one patients were identified over the 10-year period. The explosion group suffered more extensive burns, with a median % total body surface area of 31% (23.5-43.5) and 9.5% (5-20) in group 1 and group 2, respectively (P = 0.01). There was a numerically longer median hospital and intensive care unit length of stay in group 1. In multivariable analysis, there were no statistically significant predictors of intensive care unit or hospital length of stay. None of the patients appeared to have suffered any of the expected effects of primary blast wave injury. CONCLUSION: Gas bottle explosions in caravans uncommonly, if ever, result in a blast wave of sufficient energy to cause primary blast injury.

Blast-induced hearing loss suppresses hippocampal neurogenesis and disrupts long term spatial memory.

Acoustic information transduced by cochlear hair cells is continuously relayed from the auditory pathway to other sensory, motor, emotional and cognitive centers in the central nervous system. Human epidemiological studies have suggested that hearing loss is a risk factor for dementia and cognitive decline, but the mechanisms contributing to these memory and cognitive impairments are poorly understood. To explore these issues in a controlled experimental setting, we exposed adult rats to a series of intense blast wave exposures that significantly reduced the neural output of the cochlea. Several weeks later, we used the Morris Water Maze test, a hippocampal-dependent memory task, to assess the ability of Blast Wave and Control rats to learn a spatial navigation task (memory acquisition) and to remember what they had learned (spatial memory retention) several weeks earlier. The elevated plus maze and open field arena were used to test for anxiety-like behaviors. Afterwards, hippocampal cell proliferation and neurogenesis were evaluated using bromodeoxyuridine (BrdU), doublecortin (DCX), and Neuronal Nuclei (NeuN) immunolabeling. The Blast Wave and Control rats learned the spatial navigation task equally well and showed no differences on tests of anxiety. However, the Blast Wave rats performed significantly worse on the spatial memory retention task, i.e., remembering where they had been two weeks earlier. Deficits on the spatial memory retention task were associated with significant decreases in hippocampal cell proliferation and neurogenesis. Our blast wave results are consistent with other experimental manipulations that link spatial memory retention deficits (long term memory) with decreased cell proliferation and neurogenesis in the hippocampus. These results add to the growing body of knowledge linking blast-induced cochlear hearing loss with the cognitive deficits often seen in combat personnel and provide mechanistic insights into these extra auditory disorders that could lead to therapeutic interventions.

Using Gas-Driven Shock Tubes to Produce Blast Wave Signatures.

The increased incidence of improvised explosives in military conflicts has brought about an increase in the number of traumatic brain injuries (TBIs) observed. Although physical injuries are caused by shrapnel and the immediate blast, encountering the blast wave associated with improvised explosive devices (IEDs) may be the cause of traumatic brain injuries experienced by warfighters. Assessment of the effectiveness of personal protective equipment (PPE) to mitigate TBI requires understanding the interaction between blast waves and human bodies and the ability to replicate the pressure signatures caused by blast waves. Prior research has validated compression-driven shock tube designs as a laboratory method of generating representative pressure signatures, or Friedlander-shaped blast profiles; however, shock tubes can vary depending on their design parameters and not all shock tube designs generate acceptable pressure signatures. This paper presents a comprehensive numerical study of the effects of driver gas, driver (breech) length, and membrane burst pressure of a constant-area shock tube. Discrete locations in the shock tube were probed, and the blast wave evolution in time at these points was analyzed to determine the effect of location on the pressure signature. The results of these simulations are used as a basis for suggesting guidelines for obtaining desired blast profiles.