Modeling Highly Repetitive Low-level Blast Exposure in Mice.

Exposure to explosive blasts is a significant risk factor for brain trauma among exposed persons. Although the effects of large blasts on the brain are well understood, the effects of smaller blasts such as those that occur during military training are less understood. This small, low-level blast exposure also varies highly according to military occupation and training tempo, with some units experiencing few exposures over the course of several years whereas others experience hundreds within a few weeks. Animal models are an important tool in identifying both the injury mechanisms and long-term clinical health risks following low-level blast exposure. Models capable of recapitulating this wide range of exposures are necessary to inform acute and chronic injury outcomes across these disparate risk profiles. Although outcomes following a few low-level blast exposures are easily modeled for mechanistic study, chronic exposures that occur over a career may be better modeled by blast injury paradigms with repeated exposures that occur frequently over weeks and months. Shown here are methods for modeling highly repetitive low-level blast exposure in mice. The procedures are based on established and widely used pneumatic shocktube models of open-field blast exposure that can be scaled to adjust the overpressure parameters and the number or interval of the exposures. These methods can then be used to either enable mechanistic investigations or recapitulate the routine blast exposures of clinical groups under study.

Silencing CD28 attenuated chest blast exposure-induced traumatic brain injury through the PI3K/AKT/NF-κB signaling pathway in male mice.

In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100ß and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.

Our experience with blast and gunshot induced traumatic vascular injuries at Somalia's major vascular referral center.

Blast and gunshot-induced penetrating traumatic vascular injuries represent a significant portion of patients with vascular trauma in countries where there are higher rates of war-related violence. These injuries are especially challenging in resource-limited countries due to early diagnosis and transfer delays. This report aimed to present our experience regarding the surgical management and outcome of such injuries at a major referral vascular surgery centre in the country. A retrospective descriptive review of 326 patients with blast and gunshot-induced penetrating traumatic vascular injuries managed during a five-year period between April 2018 and April 2023. The demographics, mechanism of injury, type of vascular injury, Anatomical location, time to the operation, length of hospital stay, amount of blood products given, concomitant neuroskeletal injuries, development of Vascular injury associated acute kidney injury, surgical procedures performed and patient outcome were reviewed. In this study, 326 patients with 445 vascular injuries fulfilled the inclusion criteria. Most of the patients were male 92.3%, and the mean age was 28.3 ± 9.9 years. The gunshot mechanism of vascular injury was implicated in 76.1% of the injuries, and explosive-induced injury was 78 (23.9%). 193 (59.2%) of the patients had isolated arterial injuries, 117 (35.9%) patients had combined arterial and venous injuries while 18 (4.9%) patients had isolated venous injuries. The most commonly injured arteries were the femoral artery, followed by Brachial and popliteal artery injuries (26.1%, 23.5% and 19.4%, respectively). The median time to revascularization was 8.8 ± 8.7 h. 46.8% of the patients had Concomitant fractures, while 26.5% had Concomitant nerve injuries. Only three patients had temporary non-heparin-bound shunts during their arrival. The most common surgical intervention in arterial injuries was reversed saphenous vein graft 46.1%. The mortality was 5.8% and 7.7% of the patients needed secondary amputation. The majority of wartime arterial injuries are a result of Blast and gunshot vascular injuries. Frequent need for autologous vein grafts should be considered to manage such injuries. Results are encouraging despite delays in intervention; therefore, all viable limbs should be revascularized, keeping in mind the long-term functionality of the limb.

Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

Effect of blast orientation, multi-point blasts, and repetitive blasts on brain injury.

Explosions in the battlefield can result in brain damage. Research on the effects of shock waves on brain tissue mainly focuses on the effects of single-orientation blast waves, while there have been few studies on the dynamic response of the human brain to directional explosions in different planes, multi-point explosions and repetitive explosions. Therefore, the brain tissue response and the intracranial pressure (ICP) caused by different blast loadings were numerically simulated using the CONWEP method. In the study of the blast in different directions, the lateral explosion blast wave was found to cause greater ICP than did blasts from other directions. When multi-point explosions occurred in the sagittal plane simultaneously, the ICP in the temporal lobe increased by 37.8 % and the ICP in the parietal lobe decreased by 17.6 %. When multi-point explosions occurred in the horizontal plane, the ICP in the frontal lobe increased by 61.8 % and the ICP in the temporal lobe increased by 12.2 %. In a study of repetitive explosions, the maximum ICP of the second blast increased by 40.6 % over that of the first blast, and that of the third blast increased by 61.2 % over that of the second blast. The ICP on the brain tissue from repetitive blasts can exceed 200 % of that of a single explosion blast wave.

[Features of otosurgery in children after blast injuries]. / Osobennosti rekonstruktivnoi otokhirurgii u detei posle minno-vzryvnykh ranenii.

An explosion is a process that rapidly releases a huge amount of energy in the form of heat, kinetic energy, and high-pressure shock waves. Since the organ of hearing is most susceptible to pressure changes, damage to the sound-conducting or sound-receiving systems is inevitable in case of an explosive injury. This article examines the mechanism of formation of explosive injuries of the middle and inner ear in children and adolescents, the features of diagnosis and tactics of surgical reconstructive treatment of explosive ear injuries based on the data available in the scientific literature and their own experience.

The dynamic response of human lungs due to underwater shock wave exposure.

Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the most vulnerable organs, namely the lungs, existing criteria are highly variable due to insufficient human data and the corresponding inability to understand the underlying injury mechanisms. This study presents an experimental characterization of isolated human lung dynamics during simulated exposure to underwater shock waves. We found that the large acoustic impedance at the surface of the lung severely attenuated transmission of the shock wave into the lungs. However, the shock wave initiated large bulk pressure-volume cycles that are distinct from the response of the solid organs under similar loading. These pressure-volume cycles are due to compression of the contained gas, which we modeled with the Rayleigh-Plesset equation. The extent of these lung dynamics was dependent on physical confinement, which in real underwater blast conditions is influenced by factors such as rib cage properties and donned equipment. Findings demonstrate a potential causal mechanism for implosion injuries, which has significant implications for the understanding of primary blast lung injury due to underwater blast exposures.

Methemoglobinemia screening and treatment in tank warfare survivors.

INTRODUCTION: Methemoglobinemia, characterized by the conversion of functional hemoglobin to methemoglobin, can significantly impede tissue oxygenation. Prompt diagnosis and treatment of methemoglobinemia are critical to optimizing clinical outcomes. Although the underlying etiology of methemoglobinemia is often attributed to a medication reaction or chemical exposure, its association with battlefield trauma remains underexplored. This case series explores the presence of methemoglobinemia in nine soldiers evacuated from tanks targeted by explosives, shedding new light on screening needs and treatment strategies. CASES DESCRIPTION: Nine combat trauma patients with methemoglobinemia were admitted to Soroka Medical Center over a two-month period. Detailed case descriptions illustrate the diverse presentations and treatment responses. Notably, the administration of methylene blue resulted in rapid methemoglobin reductions and an improvement in oxygenation without any observed side effects. DISCUSSION: This series highlights an unexpected consequence of an explosion within an armored fighting vehicle and the challenges related to standard pulse oximetry interpretation and accuracy in the presence of methemoglobinemia, emphasizing the need for vigilant monitoring and co-oximetry utilization. Additionally, the coexistence of carboxyhemoglobin further warrants attention due to its synergistic and deleterious effects on oxygen delivery. Collaborative efforts with military authorities should aim to explore the underlying mechanisms associated with trauma and methemoglobinemia and optimize battlefield care. CONCLUSION: This case series underscores the significance of methemoglobinemia screening in combat trauma patients, and advocates for systematic co-oximetry utilization and methylene blue availability in combat zones. Early detection and intervention of methemoglobinemia in combat soldiers are often difficult in the context of battlefield injuries but are necessary to mitigate the potentially fatal consequences of this condition.

Blast injury: Impact to the cornea.

Visual disorders are common even after mild traumatic brain injury (mTBI) or blast exposure. The cost of blast-induced vision loss in civilians, military personnel, and veterans is significant. The visual consequences of blasts associated with TBI are elusive. Active military personnel and veterans report various ocular pathologies including corneal disorders post-combat blasts. The wars and conflicts in Afghanistan, Iraq, Syria, and Ukraine have significantly increased the number of corneal and other ocular disorders among military personnel and veterans. Binocular vision, visual fields, and other visual functions could be impaired following blast-mediated TBI. Blast-associated injuries can cause visual disturbances, binocular system problems, and visual loss. About 25% of veterans exposed to blasts report corneal injury. Blast exposure induces corneal edema, corneal opacity, increased corneal thickness, damage of corneal epithelium, corneal abrasions, and stromal and endothelial abnormality including altered endothelial density, immune cell infiltration, corneal neovascularization, Descemet membrane rupture, and increased pain mediators in animal models and the blast-exposed military personnel including veterans. Immune response exacerbates blast-induced ocular injury. TBI is associated with dry eyes and pain in veterans. Subjects exposed to blasts that cause TBI should undergo immediate clinical visual and ocular examinations. Delayed visual care may lead to progressive vision loss, lengthening/impairing rehabilitation and ultimately may lead to permanent vision problems and blindness. Open-field blast exposure could induce corneal injuries and immune responses in the cornea. Further studies are warranted to understand corneal pathology after blast exposure. A review of current advancements in blast-induced corneal injury will help elucidate novel targets for potential therapeutic options. This review discusses the impact of blast exposure-associated corneal disorders.

Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

Contemporary History of Spine Fractures Following Deck-Slap Injury: From Deck Blast During World War II Naval Battles to Axial Trauma During Touristic Speedboat Sea Cruise in 21st Century.

In large-scale naval battles during World War II, sailors sometimes sustained serious lower limb injuries when explosion blast of sea mines was transmitted from underneath through the metal deck of the ships. Some of these sailors were thrown in the air due to the blast and sustained axial trauma of the spine when they landed on the hard deck, which was thus called a deck slap by Captain Joseph Barr in 1946, among others. Nowadays, this peculiar mechanism has shifted to the civilian setting. Tourists unaware of the danger may sustain spine compression fractures when they sit at the bow of speed boats while underway on a calm sea. When the craft unexpectedly crosses the wake of another ship, tourists are thrown a few feet in the air before suffering a hard landing on their buttocks. This historical vignette is presented as a preventive message to help to reduce this poorly known yet avoidable "summer wave of vertebral fractures."

Risk of burns in pressure cooker usage: a comprehensive analysis of explosive injuries.

BACKGROUND: Despite the widespread use of pressure cookers for quick and efficient cooking, literature has insufficiently highlighted the potential dangers resulting from inappropriate handling. This study aims to provide a comprehensive overview of 32 patients who presented with pressure cooker burns, emphasizing the serious risks associated with their misuse. METHODS: Retrospective data were collected from patients admitted to Bagcilar Training and Research Hospital Burn Center between 2017 and 2020 with pressure cooker burns in Türkiye. Data encompassed patient characteristics, burn causes, locations, severities, treatments, and clinical outcomes. RESULTS: The study included 32 patients (29 female/3 male) with a mean age of 42.3 (8-83). Patients were categorized based on burn areas, revealing associated injuries such as ocular (34.3%) and ear injuries (6.25%). The average hospital stay was 10.5 days [2-37]. While five pressure cookers exploded due to product-related issues, 26 explosions resulted from user errors (15.6%/81.2%). Importantly, no mortality was observed among the patients. CONCLUSION: While pressure cookers facilitate rapid food preparation, this study underscores the severe risks arising from product or usage errors. This study emphasizes the need for more effective usage instructions and increased awareness about pressure cookers to prevent burn risks. We anticipate that educational programs focused on safe pressure cooker use could significantly reduce the incidence of serious injuries.

Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans.

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.

Weight-Drop Method for Inducing Closed Head Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50-450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.