Primary Blast Effects Research Articles

Case Report and Literature Review: A Severe Case of Blast-Related Traumatic Brain Injury

AbstractBlast-related traumatic brain injuries (bTBIs), once considered the signature wound of wars, have increasingly affected civilian populations due to the rise in terrorist attacks and industrial accidents. These injuries are complex, resulting from a combination of primary blast effects, secondary projectiles, tertiary impacts, and quaternary injuries from burns and toxic gas inhalation. Understanding the clinical presentation, management strategies, and outcomes of bTBIs is essential for enhancing patient care and improving prognosis. We report a case of industrial-related severe bTBI with opened depressed skull fracture and intracranial hematoma. The patient underwent decompressive craniectomy and evacuation of clot but postoperatively had a stormy recovery and multiple complications. He eventually succumbed due to his complications. This underscores the complexity of bTBIs and highlights the importance of a multidisciplinary approach in the management of bTBIs. Further research is needed to optimize treatment protocols and rehabilitation strategies for individuals with bTBIs.

Intact peritoneum in a child with ileal perforation from a firearm injury

Introduction Indirect intra-abdominal injury with an intact peritoneum following close passage of highly energized projectiles is an uncommon but clearly described phenomenon; likewise delayed gastrointestinal perforation hours or days after passage of a high-energy stress wave from primary blast injury is uncommon. Awareness of these two rare occurrences is required to ensure delayed perforations are diagnosed and managed in a timely manner. Case report An 8-year-old male child sustained a shotgun injury to the right elbow and the abdominal wall only of the right hypochondrium. Due to a non-salvageable joint injury, he underwent amputation of the right upper limb above the elbow, but on the third day of admission, he developed peritonitis and an X-ray revealed pneumoperitoneum. On abdominal exploration, two small ileal perforations were found without penetration of the peritoneum or diaphragm. The ileal injuries were primarily repaired and the postoperative course was uneventful. Conclusion Indirect injury to abdominal viscera from the primary blast effect of close passage of high-energy projectiles resulting is rare and can have significant consequences if not diagnosed and managed early.

Relationship Between Headache Characteristics and a Remote History of TBI in Veterans: A 10-Year Retrospective Chart Review.

Background and ObjectivesThe objective of this work was to examine the association between deployment-related traumatic brain injury (TBI) severity, frequency, and other injury characteristics with headache outcomes in veterans evaluated at a Veterans Administration (VA) polytrauma support clinic.MethodsWe conducted a retrospective chart review of 594 comprehensive TBI evaluations between 2011 and 2021. Diagnostic criteria were based on the Department of Defense/VA Consensus-Based Classification of Closed TBI. Adjusted odds ratios (AORs) and 95% CIs were estimated for headache prevalence (logistic), headache severity (ordinal), and prevalence of migraine-like features (logistic) with multiple regression analysis. Regression models were adjusted for age, sex, race/ethnicity, time since injury, and mental health diagnoses.ResultsTBI severity groups were classified as sub concussive exposure (n = 189) and mild (n = 377), moderate (n = 28), and severe TBI (n = 0). Increased headache severity was reported in veterans with mild TBI (AOR 1.72 [95% CI 1.15, 2.57]) and moderate TBI (AOR 3.89 [1.64, 9.15]) compared to those with subconcussive exposure. A history of multiple mild TBIs was associated with more severe headache (AOR 2.47 [1.34, 4.59]) and migraine-like features (AOR 5.95 [2.55, 13.77]). No differences were observed between blast and nonblast injuries; however, greater headache severity was reported in veterans with both primary and tertiary blast effects (AOR 2.56 [1.47, 4.49]). Alteration of consciousness (AOC) and posttraumatic amnesia (PTA) >30 minutes were associated with more severe headache (AOR 3.37 [1.26, 9.17] and 5.40 [2.21, 13.42], respectively). The length of time between the onset of last TBI and the TBI evaluation was associated with headache severity (AOR 1.09 [1.02, 1.17]) and prevalence of migraine-like features (AOR 1.27 [1.15, 1.40]). Last, helmet use was associated with less severe headache (AOR 0.42 [0.23, 0.75]) and lower odds of migraine-like features (AOR 0.45 [0.21, 0.98]).DiscussionOur data support the notion of a dose-response relationship between TBI severity and headache outcomes. A history of multiple mild TBIs and longer duration of AOC and PTA are unique risk factors for poor headache outcomes in veterans. Furthermore, this study sheds light on the poor headache outcomes associated with subconcussive exposure. Past TBI characteristics should be considered when developing headache management plans for veterans.

Effect of blast loading on the risk of rib fractures: a preliminary 3D numerical investigation

Blast is a complex phenomenon which needs to be understood, especially in a military framework, where this kind of loading can have severe consequences on the human body. Indeed, the literature lists a number of studies which try to investigate the dangerousness of such a phenomenon, both at experimental and numerical level, and the injuries that could occur when the fighters or police officers are stroke by blast wave. When focusing on primary blast effect, this paper analyses the effect of this loading on the occurrence of rib fracture, using previously developed injury risk curves.

Design and Analysis of Vehicle Mine Blast Using AUTODYN

Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or completely destroying a lighter vehicle. The most common form of AV mine is the blast mine, which uses a large amount of explosive to directly damage the target. In a conventional military setting, landmines are used as a defensive force-multiplier and to restrict the movements of the opposing force. They are relatively cheap to purchase and easy to acquire, hence landmines are also potent weapons in the insurgents’ armamentarium. The stand-off nature of its design has allowed insurgents to cause significant injuries to security forces in current conflicts with little personal risk. As a result, AV mines and improvised explosive devices (IEDs) have become the most common cause of death and injury to Coalition and local security forces operation. A number of different strategies are required to mitigate the blast effects of an explosion. Primary blast effects can be reduced by increasing the standoff distance between the seat of the explosion and the crew compartment. Enhancement of armour on the base of the vehicle, as well as improvements in personal protection can prevent penetration of fragments. Mitigating tertiary effects can be achieved by altering the vehicle geometry and structure, increasing vehicle mass, as well as developing new strategies to reduce the transfer of the impulse through the vehicle to the occupants. Protection from thermal injury can be provided by incorporating fire resistant materials into the vehicle and in personal clothing. The challenge for the vehicle designer is the incorporation of these protective measures within an operationally effective platform.

Sex as a Biological Variable in Preclinical Modeling of Blast-Related Traumatic Brain Injury

Approaches to furthering our understanding of the bioeffects, behavioral changes, and treatment options following exposure to blast are a worldwide priority. Of particular need is a more concerted effort to employ animal models to determine possible sex differences, which have been reported in the clinical literature. In this review, clinical and preclinical reports concerning blast injury effects are summarized in relation to sex as a biological variable (SABV). The review outlines approaches that explore the pertinent role of sex chromosomes and gonadal steroids for delineating sex as a biological independent variable. Next, underlying biological factors that need exploration for blast effects in light of SABV are outlined, including pituitary, autonomic, vascular, and inflammation factors that all have evidence as having important SABV relevance. A major second consideration for the study of SABV and preclinical blast effects is the notable lack of consistent model design—a wide range of devices have been employed with questionable relevance to real-life scenarios—as well as poor standardization for reporting of blast parameters. Hence, the review also provides current views regarding optimal design of shock tubes for approaching the problem of primary blast effects and sex differences and outlines a plan for the regularization of reporting. Standardization and clear description of blast parameters will provide greater comparability across models, as well as unify consensus for important sex difference bioeffects.

Effects on Neurons and Hippocampal Slices by Single and Multiple Primary Blast Pressure Waves From Detonating Spherical Cyclotrimethylenetrinitramine (RDX) Explosive Charges.

Threshold shock-impulse levels required to induce cellular injury and cumulative effects upon single and/or multiple exposures are not well characterized. Currently, there are few in vitro experimental models with blast pressure waves generated by using real explosives in the laboratory for investigating the effects of primary blast-induced traumatic brain injury. An in vitro indoor experimental platform is developed using real military explosive charges to accurately represent battlefield blast exposure and to probe the effects of primary explosive blast on dissociated neurons and tissue slices. Preliminary results indicate that physical insults altered membrane permeability, impacted cellular viability, created axonal beadings, and led to synaptic protein loss in hippocampal slice cultures. Injuries from blast under the conditions that were examined did not appear to cause immediate or sustained damage to the cells. Three consecutive primary blasts failed to disrupt the overall cellular integrity in the hippocampal slice cultures and produced a unique type of pathology comprised with distinct reduction in synaptic proteins before cellular deterioration set in. These observed changes might add to the challenges in regard to enhancing our understanding of the complex biochemical and molecular mechanisms caused by primary blast-induced injury.

Nanometer ultrastructural brain damage following low intensity primary blast wave exposure.

Blast-induced mild traumatic brain injury (mTBI) is of particular concern among military personnel due to exposure to blast energy during military training and combat. The impact of primary low-intensity blast mediated pathophysiology upon later neurobehavioral disorders has been controversial. Developing a military preclinical blast model to simulate the pathophysiology of human blast injury is an important first step. This article provides an overview of primary blast effects and perspectives of our recent studies demonstrating ultrastructural changes in the brain and behavioral disorders resulting from open-field blast exposures up to 46.6 kPa using a murine model. The model is scalable and permits exposure to varying magnitudes of primary blast injuries by placing animals at different distances from the blast center or by changing the amount of C4 charge. We here review the implications and future applications and directions of using this animal model to uncover the underlying mechanisms related to primary blast injury. Overall, these studies offer the prospect of enhanced understanding of the pathogenesis of primary low-intensity blast-induced TBI and insights for prevention, diagnosis and treatment of blast induced TBI, particularly mTBI/concussion related to current combat exposures.

Evaluating Primary Blast Effects In Vitro.

Exposure to blast events can cause severe trauma to vital organs such as the lungs, ears, and brain. Understanding the mechanisms behind such blast-induced injuries is of great importance considering the recent trend towards the use of explosives in modern warfare and terrorist-related incidents. To fully understand blast-induced injury, we must first be able to replicate such blast events in a controlled environment using a reproducible method. In this technique using shock tube equipment, shock waves at a range of pressures can be propagated over live cells grown in 2D, and markers of cell viability can be immediately analyzed using a redox indicator assay and the fluorescent imaging of live and dead cells. This method demonstrated that increasing the peak blast overpressure to 127 kPa can stimulate a significant drop in cell viability when compared to untreated controls. Test samples are not limited to adherent cells, but can include cell suspensions, whole-body and tissue samples, through minor modifications to the shock tube setup. Replicating the exact conditions that tissues and cells experience when exposed to a genuine blast event is difficult. Techniques such as the one presented in this article can help to define damage thresholds and identify the transcriptional and epigenetic changes within cells that arise from shock wave exposure.

High-speed imaging and small-scale explosive characterization techniques to understand effects of primary blast-induced injury on nerve cell structure and function

Traumatic brain injury (TBI) is often associated with blast exposure. Even in the absence of penetrating injury or evidence of tissue injury on imaging, blast TBI may trigger a series of neural/glial cellular and functional changes. Unfortunately, the diagnosis and proper treatment of mild traumatic brain injury (mTBI) caused by explosive blast is challenging, as it is not easy to clinically distinguish blast from non-blast TBI on the basis of patient symptoms. Damage to brain tissue, cell, and subcellular structures continues to occur slowly and in a manner undetectable by conventional imaging techniques. The threshold shock impulse levels required to induce damage and the cumulative effects upon multiple exposures are not well characterized. Understanding how functional and structural damage from realistic blast impact at cellular and tissue levels at variable timescales after mTBI events may be vital for understanding this injury phenomenon and for linking mechanically induced structural changes with measurable effects on the nervous system. Our working hypothesis is that there is some transient physiological dysfunction occurring at cellular and subcellular levels within the central nervous system due to primary blast exposure. We have developed a novel in vitro indoor experimental system that uses real military explosive charges to more accurately represent military blast exposure and to probe the effects of primary explosive blast on dissociated neurons. We believe this system offers a controlled experimental method to analyze and characterize primary explosive blast-induced cellular injury and to understand threshold injury phenomenon. This paper will also focus on the modeling aspect of our work and how it relates to the experimental work.

Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast

Due to recent military conflicts and terrorist attacks, blast-induced traumatic brain injury (bTBI) presents a health concern for military and civilian personnel alike. Although secondary blast (penetrating injury) and tertiary blast (inertia-driven brain deformation) are known to be injurious, the effects of primary blast caused by the supersonic shock wave interacting with the skull and brain remain debated. Our group previously reported that in vitro primary blast exposure reduced long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) and that primary blast affects key proteins governing LTP. Recent studies have investigated phosphodiesterase-4 (PDE4) inhibition as a therapeutic strategy for reducing LTP deficits following inertia-driven TBI. We investigated the therapeutic potential of PDE4 inhibitors, specifically roflumilast, to ameliorate primary blast-induced deficits in LTP. We found that roflumilast at concentrations of 1nM or greater prevented deficits in neuronal plasticity measured 24h post-injury. We also observed a therapeutic window of at least 6h, but <23h. Additionally, we investigated molecular mechanisms that could elucidate this therapeutic effect. Roflumilast treatment (1nM delivered 6h post-injury) significantly increased total AMPA glutamate receptor 1 (GluR1) subunit expression, phosphorylation of the GluR1 subunit at the serine-831 site, and phosphorylation of stargazin at the serine-239/240 site upon LTP induction, measured 24h following injury. Roflumilast treatment significantly increased PSD-95 regardless of LTP induction. These findings indicate that further investigation into the translation of PDE4 inhibition as a therapy following bTBI is warranted.

Explosive Blast Loading on Human 3D Aggregate Minibrains.

The effects of primary explosive blast on brain tissue still remain mostly unknown. There are few in vitro models that use real explosives to probe the mechanisms of injury at the cellular level. In this work, 3D aggregates of human brain cells or brain microphysiological system were exposed to military explosives at two different pressures (50 and 100psi). Results indicate that membrane damage and oxidative stress increased with blast pressure, but cell death remained minimal.

Primary Blast Injury Depressed Hippocampal Long-Term Potentiation through Disruption of Synaptic Proteins.

Blast-induced traumatic brain injury (bTBI) is a major threat to United States service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal function.

The Effect of Underwater Blast on Aggregating Brain Cell Cultures.

Although the deleterious effects of primary blast on gas-filled organs are well accepted, the effect of blast-induced shock waves on the brain is less clear because of factors that complicate the interpretation of clinical and experimental data. Brain cell aggregate cultures are comprised of multiple differentiated brain cell types and were used to examine the effects of underwater blast. Suspensions of these cultures encased in dialysis tubing were exposed to explosive-generated underwater blasts of low (∼300 kPa), medium (∼2,700 kPa), or high (∼14,000 kPa) intensities and harvested at 1-28 days post-exposure. No changes in gross morphology were noted immediately or weeks after blast wave exposure, and no increases in either apoptotic (caspase-3) or necrotic (lactate dehydrogenase) cell death were observed. Changes in neuronal (neurofilament H, acetylcholinesterase, and choline acetyltransferase) and glial (glial fibrillary acidic protein, glutamine synthetase) endpoints did not occur. However, significant time- and pressure-related increases in Akt (protein kinase B) phosphorylation were noted, as well as declines in vascular endothelial growth factor levels, implicating pathways involved in cellular survival mechanisms. The free-floating nature of the aggregates during blast wave exposure, coupled with their highly hydrolyzed dialysis tubing containment, results in minimized boundary effects, thus enabling accurate assessment of brain cell response to a simplified shock-induced stress wave. This work shows that, at its simplest, blast-induced shock waves produce subtle changes in brain tissue. This study has mechanistic implications for the study of primary blast-induced traumatic brain injury and supports the thesis that underwater blast may cause subtle changes in the brains of submerged individuals.

Effects of repetitive low-pressure explosive blast on primary neurons and mixed cultures.

Repetitive mild traumatic brain injury represents a considerable health concern, particularly for athletes and military personnel. For blast-induced brain injury, threshold shock-impulse levels required to induce such injuries and cumulative effects with single and/or multiple exposures are not well characterized. Currently, there is no established in vitro experimental model with blast pressure waves generated by live explosives. This study presents results of primary neurons and mixed cultures subjected to our unique in vitro indoor experimental platform that uses real military explosive charges to probe the effects of primary explosive blast at the cellular level. The effects of the blast on membrane permeability, generation of reactive oxygen species (ROS), uptake of sodium ions, intracellular calcium, and release of glutamate were probed 2 and 24 hr postblast. Significant changes in membrane permeability and sodium uptake among the sham, single-blast-injured, and triple-blast-injured samples were observed. A significant increase in ROS and glutamate release was observed for the triple-blast-injured samples compared with the sham. Changes in intracellular calcium were not significant. These results suggest that blast exposure disrupts the integrity of the plasma membrane, leading to the upset of ion homeostasis, formation of ROS, and glutamate release. Published 2016. †This article is a U.S. Government work and is in the public domain in the USA.

Isolated Primary Blast Inhibits Long-Term Potentiation in Organotypic Hippocampal Slice Cultures.

Over the last 13 years, traumatic brain injury (TBI) has affected over 230,000 U.S. service members through the conflicts in Iraq and Afghanistan, mostly as a result of exposure to blast events. Blast-induced TBI (bTBI) is multi-phasic, with the penetrating and inertia-driven phases having been extensively studied. The effects of primary blast injury, caused by the shockwave interacting with the brain, remain unclear. Earlier in vivo studies in mice and rats have reported mixed results for primary blast effects on behavior and memory. Using a previously developed shock tube and in vitro sample receiver, we investigated the effect of isolated primary blast on the electrophysiological function of rat organotypic hippocampal slice cultures (OHSC). We found that pure primary blast exposure inhibited long-term potentiation (LTP), the electrophysiological correlate of memory, with a threshold between 9 and 39 kPa·ms impulse. This deficit occurred well below a previously identified threshold for cell death (184 kPa·ms), supporting our previously published finding that primary blast can cause changes in brain function in the absence of cell death. Other functional measures such as spontaneous activity, network synchronization, stimulus-response curves, and paired-pulse ratios (PPRs) were less affected by primary blast exposure, as compared with LTP. This is the first study to identify a tissue-level tolerance threshold for electrophysiological changes in neuronal function to isolated primary blast.

High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves.

In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI.

Prediction of globe rupture caused by primary blast: a finite element analysis

Although a human eye comprises less than 0.1% of the frontal body surface area, injuries to the eye are found to be disproportionally common in survivors of explosions. This study aimed to introduce a Lagrangian–Eulerian coupling model to predict globe rupture resulting from primary blast effect. A finite element model of a human eye was created using Lagrangian mesh. An explosive and its surrounding air domain were modelled using Eulerian mesh. Coupling the two models allowed simulating the blast wave generation, propagation and interaction with the eye. The results showed that the peak overpressures caused by blast wave on the corneal apex are 2080, 932.1 and 487.3 kPa for the victim distances of 0.75, 1.0 and 1.25 m, respectively. Higher stress occurred at the limbus, where the peaks for the three victim distances are 25.5, 14.1 and 6.4 MPa. The overpressure threshold of globe rupture was determined as 2000 kPa in a small-scale explosion. The findings would provide insights into the mechanism of primary blast-induced ocular injuries.

Galveston Brain Injury Conference 2010: Clinical and Experimental Aspects of Blast Injury

Blast injury is the most prevalent source of mortality and morbidity among combatants in Operations Iraqi and Enduring Freedom. Blast-induced neurotrauma (BINT) is a common cause of mortality, and even mild BINT may be associated with chronic cognitive and emotional deficits. In addition to military personnel, the increasing use of explosives by terrorists has resulted in growing numbers of blast injuries in civilian populations. Since the medical and rehabilitative communities are likely to be faced with increasing numbers of patients suffering from blast injury, the 2010 Galveston Brain Injury Conference focused on topics related to the diagnosis, treatment, and mechanisms of BINT. Although past military actions have resulted in large numbers of blast casualties, BINT is considered the signature injury of the conflicts in Iraq and Afghanistan. The attention focused on BINT has led to increased financial support for research on blast effects, contributing to the development of better experimental models of blast injury and a clearer understanding of the mechanisms of BINT. This more thorough understanding of blast injury mechanisms will result in novel and more effective therapeutic and rehabilitative strategies designed to reduce injury and facilitate recovery, thereby improving long-term outcomes in patients suffering from the devastating and often lasting effects of BINT. The following is a summary of the 2010 Galveston Brain Injury Conference, that included presentations related to the diagnosis and treatment of acute BINT, the evaluation of the long-term neuropsychological effects of BINT, summaries of current experimental models of BINT, and a debate about the relative importance of primary blast effects on the acute and long-term consequences of blast exposure.

Indirect Colonic Injury After Military Wounding: A Case Series

Colonic trauma in wartime most commonly results from direct injury along the path of a penetrating missile. Rarely, the colon may be injured by primary blast effect or by propagation of energy by the missile, remote from the track of the projectile. This article describes the clinical presentation and operative findings in five patients who sustained high energy-transfer gunshot wounds (GSWs) or fragmentation injuries from blast who were found to have sustained colonic injuries anatomically remote from the missile track/s. Military surgeons should be aware of the phenomenon of indirect injury to the colon after high-energy transfer GSW and blast injury. A high index of suspicion should be maintained and cross-sectional imaging used where feasible. Primary colonic reconstruction was used safely in these patients with indirect colonic injuries.