-
Acta Neuropathologica Communications Jun 2022Low-level blast exposure can result in neurological impairment for military personnel. Currently, there is a lack of experimental data using sex as a biological variable...
Low-level blast exposure can result in neurological impairment for military personnel. Currently, there is a lack of experimental data using sex as a biological variable in neurovascular outcomes following blast exposure. To model mild blast traumatic brain injury (mbTBI), male and female rats were exposed to a single 11 psi static peak overpressure blast wave using the McMillan blast device and cohorts were then euthanized at 6 h, 24 h, 7 d and 14 d post-blast followed by isolation of the amygdala. After mbTBI, animals experience immediate bradycardia, although no changes in oxygen saturation levels or weight loss are observed. Male mbTBI animals displayed significantly higher levels of anxiety-like behavior (open field and elevated plus maze) compared to male sham groups; however, there was no anxiety phenotype in female mbTBI animals. Blast-induced neurovascular damage was explored by measuring expression of tight junction (TJ) proteins (zonula occludens-1 (ZO-1), occludin and claudin-5), glial fibrillary acidic protein (GFAP) and astrocyte end-feet coverage around the blood-brain barrier (BBB). Western blot analysis demonstrates that TJ protein levels were significantly decreased at 6 h and 24 h post-mbTBI in male rats, but not in female rats, compared to sham. Female animals have decreased GFAP at 6 h post-mbTBI while male animals display decreased GFAP expression at 24 h post-mbTBI. By 7 d post-mbTBI, there were no significant differences in TJ or GFAP levels between groups in either sex. At 24 h post-mbTBI, vascular integrity and astrocytic end-feet coverage around the BBB was significantly decreased in males following mbTBI. These results demonstrate that loss of GFAP expression may be due to astrocytic damage at the BBB. Our findings also demonstrate sex differences in acute vascular and behavioral outcomes after single mbTBI. Female animals display a lack of BBB pathology after mbTBI corresponding to improved acute neuropsychological outcomes as compared to male animals.
Topics: Animals; Anxiety; Blast Injuries; Blood-Brain Barrier; Brain Concussion; Female; Male; Rats
PubMed: 35761393
DOI: 10.1186/s40478-022-01395-8 -
Vision Research Sep 2021While chronic visual symptom complaints are common among Veterans with a history of mild traumatic brain injury (mTBI), research is still ongoing to characterize the...
While chronic visual symptom complaints are common among Veterans with a history of mild traumatic brain injury (mTBI), research is still ongoing to characterize the pattern of visual deficits that is most strongly associated with mTBI and specifically, the impact of blast-related mTBI on visual functioning. One area that has not been well explored is the potential impact of blast mTBI on refractive error. While myopic shifts have been documented following head injuries in civilian populations, posttraumatic myopic shifts have not been explored in participants with military mTBI. This study investigated the impact of blast mTBIs on a range of visual function measures including distance acuity and refractive error, in a well-characterized cohort of thirty-one Post-9/11 veterans for whom detailed clinical interviews regarding military and TBI history were available. Seventeen participants had a history of blast-related mTBI (blast mTBI + group) while 14 did not (blast mTBI- group). Results show an increased frequency of convergence insufficiency and myopia in the blast mTBI + group relative to the blast mTBI- group. Linear regression analyses further show that deficits in distance acuity and refractive error are associated with the number of blast mTBIs during military service but not the number of non-blast mTBIs or the number of lifetime non-blast TBIs and cannot be accounted for by PTSD. These results are consistent with long-lasting damage following blast mTBI to subcortical visual structures that support both vergence movements and the accommodative functions needed to see clearly objects at varying distances.
Topics: Afghan Campaign 2001-; Blast Injuries; Brain Concussion; Humans; Iraq War, 2003-2011; Myopia; Neuropsychological Tests; Ocular Motility Disorders; Stress Disorders, Post-Traumatic
PubMed: 34000559
DOI: 10.1016/j.visres.2021.04.004 -
Behavioral and Myelin-Related Abnormalities after Blast-Induced Mild Traumatic Brain Injury in Mice.Journal of Neurotrauma Jun 2021In civilian and military settings, mild traumatic brain injury (mTBI) is a common consequence of impacts to the head, sudden blows to the body, and exposure to...
In civilian and military settings, mild traumatic brain injury (mTBI) is a common consequence of impacts to the head, sudden blows to the body, and exposure to high-energy atmospheric shockwaves from blast. In some cases, mTBI from blast exposure results in long-term emotional and cognitive deficits and an elevated risk for certain neuropsychiatric diseases. Here, we tested the effects of mTBI on various forms of auditory-cued fear learning and other measures of cognition in male C57BL/6J mice after single or repeated blast exposure (blast TBI; bTBI). bTBI produced an abnormality in the temporal organization of cue-induced freezing behavior in a conditioned trace fear test. Spatial working memory, evaluated by the Y-maze task performance, was also deleteriously affected by bTBI. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis for glial markers indicated an alteration in the expression of myelin-related genes in the hippocampus and corpus callosum 1-8 weeks after bTBI. Immunohistochemical and ultrastructural analyses detected bTBI-related myelin and axonal damage in the hippocampus and corpus callosum. Together, these data suggest a possible link between blast-induced mTBI, myelin/axonal injury, and cognitive dysfunction.
Topics: Animals; Blast Injuries; Brain Injuries, Traumatic; Cognitive Dysfunction; Disease Models, Animal; Fear; Male; Mice; Mice, Inbred C57BL; Myelin Sheath; Spatial Memory
PubMed: 33605175
DOI: 10.1089/neu.2020.7254 -
The Journal of Trauma May 2010Over the last few years, thousands of soldiers and an even greater number of civilians have suffered traumatic injuries due to blast exposure, largely attributed to... (Review)
Review
Over the last few years, thousands of soldiers and an even greater number of civilians have suffered traumatic injuries due to blast exposure, largely attributed to improvised explosive devices in terrorist and insurgent activities. The use of body armor is allowing soldiers to survive blasts that would otherwise be fatal due to systemic damage. Emerging evidence suggests that exposure to a blast can produce neurologic consequences in the brain but much remains unknown. To elucidate the current scientific basis for understanding blast-induced traumatic brain injury (bTBI), the NIH convened a workshop in April 2008. A multidisciplinary group of neuroscientists, engineers, and clinicians were invited to share insights on bTBI, specifically pertaining to: physics of blast explosions, acute clinical observations and treatments, preclinical and computational models, and lessons from the international community on civilian exposures. This report provides an overview of the state of scientific knowledge of bTBI, drawing from the published literature, as well as presentations, discussions, and recommendations from the workshop. One of the major recommendations from the workshop was the need to characterize the effects of blast exposure on clinical neuropathology. Clearer understanding of the human neuropathology would enable validation of preclinical and computational models, which are attempting to simulate blast wave interactions with the central nervous system. Furthermore, the civilian experience with bTBI suggests that polytrauma models incorporating both brain and lung injuries may be more relevant to the study of civilian countermeasures than considering models with a neurologic focus alone.
Topics: Animals; Blast Injuries; Brain Injuries; Diffusion Tensor Imaging; Disease Models, Animal; Evidence-Based Practice; Head Protective Devices; Humans; Lung Injury; Military Medicine; Military Personnel; Multiple Trauma; Terrorism; United States; Warfare
PubMed: 20453776
DOI: 10.1097/TA.0b013e3181d8956d -
Prehospital and Disaster Medicine Aug 2022Blast polytrauma is among the most serious mechanisms of injury confronted by medical providers. There are currently no specific studies or guidelines that define risk... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Blast polytrauma is among the most serious mechanisms of injury confronted by medical providers. There are currently no specific studies or guidelines that define risk factors for mortality in the context of pediatric blast injuries or describe pediatric blast injury profiles.
OBJECTIVE
The objectives of this study were to evaluate risk factors for pediatric mortality and to describe differences in injury profiles between explosions related to terrorism versus unrelated to terrorism within the pediatric population.
METHODS
A PRISMA systematic review and meta-analysis was performed where articles published from the years 2000-2021 were extracted from PubMed. Mortality and injury profile data were extracted from articles that met inclusion criteria. A bivariant unadjusted odds ratio (OR) analysis was performed to establish protective and harmful factors associated with mortality and to describe the injury profiles of blasts related to terrorism. Statistical significance was established at P < .05.
RESULTS
Thirty-eight articles were included and described a total of 222,638 unique injuries. Factors associated with increased mortality included if the explosion was related to terrorism (OR = 32.73; 95% CI, 28.80-37.21; P < .05) and if the explosion involved high-grade explosives utilized in the Global War on Terror ([GWOT] OR = 1.28; 95% CI, 1.04-1.44; P < .05). Factors associated with decreased mortality included if the patient was resuscitated in a North Atlantic Treaty Organization (NATO)-affiliated combat trauma hospital (OR = 0.48; 95% CI, 0.37-0.62; P < .05); if the explosive was fireworks (OR = 3.20×10-5; 95% CI, 2.00×10-6-5.16×10-4; P < .05); and if the explosion occurred in the United States (OR = 2.40×10-5; 95% CI, 1.51×10-6-3.87×10-4; P < .05). On average, victims of explosions related to terrorism were 10.30 years old (SD = 2.73) with 68.96% (SD = 17.58%) of victims reported as male. Comparison of victims of explosions related to terrorism revealed a higher incidence of thoracoabdominal trauma (30.2% versus 8.6%), similar incidence of craniocerebral trauma (39.5% versus 43.1%), and lower incidence of extremity trauma (31.8% versus 48.3%) compared to victims of explosions unrelated to terrorism.
CONCLUSION
Explosions related to terrorism are associated with increased mortality and unique injury profiles compared to explosions unrelated to terrorism in the pediatric population. Such findings are important for optimizing disaster medical education of pediatric providers in preparation for and management of acute sequelae of blast injuries-terror-related and otherwise.
Topics: Blast Injuries; Child; Explosions; Hospitals; Humans; Male; Multiple Trauma; Terrorism
PubMed: 35603691
DOI: 10.1017/S1049023X22000747 -
The association between blast exposure and transdiagnostic health symptoms on systemic inflammation.Neuropsychopharmacology : Official... Aug 2022Chronic elevation of systemic inflammation is observed in a wide range of disorders including PTSD, depression, and traumatic brain injury. Although previous work has...
Chronic elevation of systemic inflammation is observed in a wide range of disorders including PTSD, depression, and traumatic brain injury. Although previous work has demonstrated a link between inflammation and various diagnoses separately, few studies have examined transdiagnostic symptoms and inflammation within the same model. The objective of this study was to examine relationships between psychiatric and health variables and systemic inflammation and to determine whether mild traumatic brain injury (mTBI) and/or exposure to blast munitions moderate these relationships. Confirmatory factor analysis in a large sample (N = 357) of post-9/11 Veterans demonstrated a good fit to a four-factor model reflecting traumatic stress, affective, somatic, and metabolic latent variables. Hierarchical regression models revealed that each of the latent variables were associated with higher levels of systemic inflammation. However, the strongest relationship with inflammation emerged among those who had both war-zone blast exposures and metabolic dysregulation, even after adjusting for mental health latent variables. Exploratory analyses showed that blast exposure was associated with metabolic dysregulation in a dose-response manner, with self-reported closer blast proximity associated with the greatest metabolic dysregulation. Together, these results provide a greater understanding of the types of symptoms most strongly associated with inflammation and underscore the importance of maintaining a healthy lifestyle to reduce the impact of obesity and other metabolic symptoms on future chronic disease in younger to middle-aged Veterans.
Topics: Afghan Campaign 2001-; Blast Injuries; Humans; Inflammation; Iraq War, 2003-2011; Middle Aged; Stress Disorders, Post-Traumatic; Veterans
PubMed: 34400776
DOI: 10.1038/s41386-021-01138-8 -
International Journal of Molecular... Apr 2023Trauma-related hemorrhagic shock (HS) remains a leading cause of death among military and civilian trauma patients. We have previously shown that administration of...
Trauma-related hemorrhagic shock (HS) remains a leading cause of death among military and civilian trauma patients. We have previously shown that administration of complement and HMGB1 inhibitors attenuate morbidity and mortality 24 h after injury in a rat model of blast injury (BI) and HS. To further validate these results, this study aimed to develop a swine model and evaluate BI+HS-induced pathophysiology. Anesthetized Yucatan minipigs underwent combined BI and volume-controlled hemorrhage. After 30 min of shock, animals received an intravenous bolus of PlasmaLyte A and a continuous PlasmaLyte A infusion. The survival rate was 80% (4/5), and the non-survivor expired 72 min post-BI. Circulating organ-functional biomarkers, inflammatory biomarkers, histopathological evaluation, and CT scans indicated evidence of multiple-organ damage, systemic innate immunological activation, and local tissue inflammation in the injured animals. Interestingly, a rapid and dramatic increase in plasma levels of HMGB1 and C3a and markedly early myocarditis and encephalitis were associated with early death post-BI+HS. This study suggests that this model reflects the immunopathological alterations of polytrauma in humans during shock and prolonged damage control resuscitation. This experimental protocol could be helpful in the assessment of immunological damage control resuscitation approaches during the prolonged care of warfighters.
Topics: Humans; Rats; Animals; Swine; Blast Injuries; HMGB1 Protein; Disease Models, Animal; Swine, Miniature; Hemorrhage; Shock, Hemorrhagic
PubMed: 37108656
DOI: 10.3390/ijms24087494 -
The Journal of Trauma and Acute Care... Aug 2022Improvised explosive devices have resulted in a unique polytrauma injury pattern termed dismounted complex blast injury (DCBI), which is frequent in the modern military...
BACKGROUND
Improvised explosive devices have resulted in a unique polytrauma injury pattern termed dismounted complex blast injury (DCBI), which is frequent in the modern military theater. Dismounted complex blast injury is characterized by extremity amputations, junctional vascular injury, and blast traumatic brain injury (bTBI). We developed a combat casualty relevant DCBI swine model, which combines hemorrhagic shock (HS) and tissue injury (TI) with a bTBI, to study interventions in this unique and devastating military injury pattern.
METHODS
A 50-kg male Yorkshire swine were randomized to the DCBI or SHAM group (instrumentation only). Those in the DCBI group were subjected to HS, TI, and bTBI. The blast injury was applied using a 55-psi shock tube wave. Tissue injury was created with bilateral open femur fractures. Hemorrhagic shock was induced by bleeding from femoral arteries to target pressure. A resuscitation protocol modified from the Tactical Combat Casualty Care guidelines simulated battlefield resuscitation for 240 minutes.
RESULTS
Eight swine underwent the DCBI model and five were allocated to the SHAM group. In the DCBI model the mean base excess achieved at the end of the HS shock was -8.57 ± 5.13 mmol·L -1 . A significant coagulopathy was detected in the DCBI model as measured by prothrombin time (15.8 seconds DCBI vs. 12.86 seconds SHAM; p = 0.02) and thromboelastography maximum amplitude (68.5 mm DCBI vs. 78.3 mm in SHAM; p = 0.0003). For the DCBI models, intracranial pressure (ICP) increased by a mean of 13 mm Hg, reaching a final ICP of 24 ± 7.7 mm Hg.
CONCLUSION
We created a reproducible large animal model to study the combined effects of severe HS, TI, and bTBI on coagulation and ICP in the setting of DCBI, with significant translational applications for the care of military warfighters. Within the 4-hour observational period, the swine developed a consistent coagulopathy with a concurrent brain injury evidenced by increasing ICP.
Topics: Animals; Blast Injuries; Blood Coagulation Disorders; Brain Injuries; Brain Injuries, Traumatic; Disease Models, Animal; Male; Resuscitation; Shock, Hemorrhagic; Swine
PubMed: 35545808
DOI: 10.1097/TA.0000000000003674 -
Blast Injury in the Spine: Dynamic Response Index Is Not an Appropriate Model for Predicting Injury.Clinical Orthopaedics and Related... Sep 2015Improvised explosive devices are a common feature of recent asymmetric conflicts and there is a persistent landmine threat to military and humanitarian personnel.... (Comparative Study)
Comparative Study Review
BACKGROUND
Improvised explosive devices are a common feature of recent asymmetric conflicts and there is a persistent landmine threat to military and humanitarian personnel. Assessment of injury risk to the spine in vehicles subjected to explosions was conducted using a standardized model, the Dynamic Response Index (DRI). However, the DRI was intended for evaluating aircraft ejection seats and has not been validated in blast conditions.
QUESTIONS/PURPOSES
We asked whether the injury patterns seen in blast are similar to those in aircraft ejection and therefore whether a single injury prediction model can be used for both situations.
METHODS
UK military victims of mounted blast (seated in a vehicle) were identified from the Joint Theatre Trauma Registry. Each had their initial CT scans reviewed to identify spinal fractures. A literature search identified a comparison population of ejected aircrew with spinal fractures. Seventy-eight blast victims were identified with 294 fractures. One hundred eighty-nine patients who had sustained aircraft ejection were identified with 258 fractures. The Kruskal-Wallis test was used to compare the population injury distributions and Fisher's exact test was used to assess differences at each spinal level.
RESULTS
The distribution of injuries between blast and ejection was not similar. In the cervical spine, the relative risk of injury was 11.5 times higher in blast; in the lumbar spine the relative risk was 2.9 times higher in blast. In the thoracic spine, the relative risk was identical in blast and ejection. At most individual vertebral levels including the upper thoracic spine, there was a higher risk of injury in the blast population, but the opposite was true between T7 and T12, where the risk was higher in aircraft ejection.
CONCLUSIONS
The patterns of injury in blast and aircraft are different, suggesting that the two are mechanistically dissimilar. At most vertebral levels there is a higher relative risk of fracture in the blast population, but at the apex of the thoracic spine and in the lower thoracic spine, there is a higher risk in ejection victims. The differences in relative risk at different levels, and the resulting overall different injury patterns, suggest that a single model cannot be used to predict the risk of injury in ejection and blast.
CLINICAL RELEVANCE
A new model needs to be developed to aid in the design of mine-protected vehicles for future conflicts.
Topics: Accidents, Aviation; Accidents, Traffic; Blast Injuries; Cervical Vertebrae; Explosions; Humans; Lumbar Vertebrae; Military Medicine; Predictive Value of Tests; Registries; Risk Assessment; Risk Factors; Spinal Fractures; Thoracic Vertebrae; Tomography, X-Ray Computed; United Kingdom
PubMed: 25828945
DOI: 10.1007/s11999-015-4281-2 -
Journal of the Royal Army Medical Corps Feb 2019Injuries sustained due to attacks from explosive weapons are multiple in number, complex in nature, and not well characterised. Blast may cause damage to the human body...
Injuries sustained due to attacks from explosive weapons are multiple in number, complex in nature, and not well characterised. Blast may cause damage to the human body by the direct effect of overpressure, penetration by highly energised fragments, and blunt trauma by violent displacements of the body. The ability to reproduce the injuries of such insults in a well-controlled fashion is essential in order to understand fully the unique mechanism by which they occur, and design better treatment and protection strategies to alleviate the resulting poor long-term outcomes. This paper reports a range of experimental platforms that have been developed for different blast injury models, their working mechanism, and main applications. These platforms include the shock tube, split-Hopkinson bars, the gas gun, drop towers and bespoke underbody blast simulators.
Topics: Animals; Biomedical Research; Blast Injuries; Computer Simulation; Explosions; Humans; Military Medicine; Pressure; Rats
PubMed: 29794172
DOI: 10.1136/jramc-2018-000966