Blast injury research models

Blast injuries are an increasing problem in both military and civilian practice. Primary blast injury to the lungs (blast lung) is found in a clinically significant proportion of casualties from explosions even in an open environment, and in a high proportion of severely injured casualties following explosions in confined spaces. Blast casualties also commonly suffer secondary and tertiary blast injuries resulting in significant blood loss. The presence of hypoxaemia owing to blast lung complicates the process of fluid resuscitation. Consequently, prolonged hypotensive resuscitation was found to be incompatible with survival after combined blast lung and haemorrhage. This article describes studies addressing new forward resuscitation strategies involving a hybrid blood pressure profile (initially hypotensive followed later by normotensive resuscitation) and the use of supplemental oxygen to increase survival and reduce physiological deterioration during prolonged resuscitation. Surprisingly, hypertonic saline dextran was found to be inferior to normal saline after combined blast injury and haemorrhage. New strategies have therefore been developed to address the needs of blast-injured casualties and are likely to be particularly useful under circumstances of enforced delayed evacuation to surgical care.     

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.     

Blast related neurotrauma: a review of cellular injury

Historically, blast overpressure is known to affect primarily gas-containing organs such as the lung and ear. More recent interests focus on its ability to cause damage to solid organs such as the brain, resulting in neurological disorders. Returning veterans exposed to blast but without external injuries are being diagnosed with mild traumatic brain injury (Warden 2006) and with cortical dysfunction (Cernak et al 1999). Decades of studies have been conducted to elucidate the effects of primary blast wave on the central nervous system. These studies were mostly concerned with systemic effects (Saljo et al 2000-2003; Kaur et al 1995-1997, 1999; Cernak et al 1996, 2001). The molecular mechanism of blast-induced neurotrauma is still poorly understood. This paper reviews studies related to primary blast injury to the nervous system, particularly at the cellular level. It starts with a general discussion of primary blast injury and blast wave physics, followed by a review of the literature related to 1) the blast wave/body interaction, 2) injuries to the peripheral nervous system, 3) injuries to the central nervous system, and 4) injury criteria. Finally, some of our preliminary data on cellular injury from in vitro and in vivo studies are presented. Specifically, we report on the effects of overpressure on astrocytes. In the discussion, possible mechanisms of blast-related brain injury are discussed, as well as the concerns and limitations of the published studies. A clearer understanding of the injury mechanisms at both the molecular and macroscopic (organ) level will lead to the development of new treatment, diagnosis and preventive measures.     

Quantitative analysis of brain microstructure following mild blunt and blast trauma

We induced mild blunt and blast injuries in rats using a custom-built device and utilized in-house diffusion tensor imaging (DTI) software to reconstruct 3-D fiber tracts in brains before and after injury (1, 4, and 7 days). DTI measures such as fiber count, fiber length, and fractional anisotropy (FA) were selected to characterize axonal integrity. In-house image analysis software also showed changes in parameters including the area fraction (AF) and nearest neighbor distance (NND), which corresponded to variations in the microstructure of Hematoxylin and Eosin (H&E) brain sections. Both blunt and blast injuries produced lower fiber counts, but neither injury case significantly changed the fiber length. Compared to controls, blunt injury produced a lower FA, which may correspond to an early onset of diffuse axonal injury (DAI). However, blast injury generated a higher FA compared to controls. This increase in FA has been linked previously to various phenomena including edema, neuroplasticity, and even recovery. Subsequent image analysis revealed that both blunt and blast injuries produced a significantly higher AF and significantly lower NND, which correlated to voids formed by the reduced fluid retention within injured axons. In conclusion, DTI can detect subtle pathophysiological changes in axonal fiber structure after mild blunt and blast trauma. Our injury model and DTI method provide a practical basis for studying mild traumatic brain injury (mTBI) in a controllable manner and for tracking injury progression. Knowledge gained from our approach could lead to enhanced mTBI diagnoses, biofidelic constitutive brain models, and specialized pharmaceutical treatments.     

Characterization of the response to primary blast injury

Lung injuries, predominantly arising from blast exposure, are a clinical problem in a significant minority of current military casualties. This special feature consists of a series of articles on lung injury. This first article examines the mechanism of the response to blast lung (primary blast injury to the lung). Subsequent articles examine the incidence of blast lung, clinical consequences and current concepts of treatment, computer (in silico) modelling of lung injury and finally chemical injuries to the lungs. Blast lung is caused by a shock wave generated by an explosion causing widespread damage in the lungs, leading to intrapulmonary haemorrhage. This, and the ensuing inflammatory response in the lung, leads to a compromise in pulmonary gas exchange and hypoxia that can worsen over several hours. There is also a characteristic cardio-respiratory effect mediated via an autonomic reflex causing apnoea (or rapid shallow breathing), bradycardia and hypotension (the latter possibly also due to the release of nitric oxide). An understanding of this response, and the way it modifies other reflexes, can help the development of new treatment strategies for this condition and for the way it influences the patient's response to concomitant injuries.     

口腔颌面部爆炸伤的研究现状

口腔颌面部爆炸伤是指由致伤物爆炸所造成的口腔颌面部组织损伤,两种主要致伤因素是冲击波和高速破片,较一般火器伤而言,爆炸伤的致伤机制及致伤特点都有不同之处。对爆炸伤害的物理机制和病理生理反应方面研究有助于改进防护及改善治疗策略。本文在简述口腔颌面部爆炸伤的致伤因素和损伤特点的基础上,着重综述了动物模型和有限元模型的研究方法及结果,旨在为以后的模型研究提供思路和参考。     

A computational model of blast loading on the human eye

Ocular injuries from blast have increased in recent wars, but the injury mechanism associated with the primary blast wave is unknown. We employ a three-dimensional fluid–structure interaction computational model to understand the stresses and deformations incurred by the globe due to blast overpressure. Our numerical results demonstrate that the blast wave reflections off the facial features around the eye increase the pressure loading on and around the eye. The blast wave produces asymmetric loading on the eye, which causes globe distortion. The deformation response of the globe under blast loading was evaluated, and regions of high stresses and strains inside the globe were identified. Our numerical results show that the blast loading results in globe distortion and large deviatoric stresses in the sclera. These large deviatoric stresses may be indicator for the risk of interfacial failure between the tissues of the sclera and the orbit.     

Mechanisms of Hearing Loss after Blast Injury to the Ear

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the body’s most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction.     

Injuries,Death, and Disability Associated with 11 Years of Conflict in Baghdad,Iraq: A Randomized Household Cluster Survey

Background

The objective of this study was to characterize injuries, deaths, and disabilities arising during 11 years of conflict in Baghdad.

Methods

Using satellite imagery and administrative population estimated size for Baghdad, 30 clusters were selected, proportionate to population size estimates. Interviews were conducted during April and May 2014 in 900 households containing 5148 persons. Details about injuries and disabilities occurring from 2003 through May 2014 and resultant disabilities were recorded.

Findings

There were 553 injuries reported by Baghdad residents, 225 of which were intentional, and 328 unintentional. For intentional injuries, the fatality rate was 39.1% and the disability rate 56.0%. Gunshots where the major cause of injury through 2006 when blasts/explosions became the most common cause and remained so through 2014. Among unintentional injuries, the fatality rate was 7.3% and the disability rate 77.1%. The major cause of unintentional injuries was falls (131) which have increased dramatically since 2008, followed by traffic related injuries (81), which have steadily increased. The proportion of injuries ending in disabilities remained fairly constant through the survey period.

Interpretation

Intentional injuries added substantially to the burden of unintentional injuries for the population. For Baghdad, the phases of the Iraqi conflict are reflected in the patterns of injuries and consequent deaths reported. The scale of injuries during conflict is most certainly under-reported. Difficulties recalling injuries in a survey covering 11 years is a limitation, but it is likely that minor injuries were under-reported more than severe injuries. The in- and out-migration of Baghdad populations likely had effects on the events reported which we could not measure or estimate. Damage to the health infrastructure and the flight of health workers may have contributed to mortality and morbidity. Civilian injuries as well as mortality should be measured during conflicts, though not currently done.     

Injury risk prediction from computational simulations of ocular blast loading

A predictive Lagrangian–Eulerian finite element eye model was used to analyze 2.27 and 0.45 kg trinitrotoluene equivalent blasts detonated from 24 different locations. Free air and ground level blasts were simulated directly in front of the eye and at lateral offset locations with box, average, less protective, and more protective orbital anthropometries, resulting in 96 simulations. Injury risk curves were developed for hyphema, lens dislocation, retinal damage, and globe rupture from experimental and computational data to compute risk from corneoscleral stress and intra-ocular pressure computational outputs. Corneoscleral stress, intra-ocular pressure, and injury risks increased when the blast size was larger and located nearer to the eye. Risks ranged from 20–100 % for hyphema, 1–100 % for lens dislocation, 2–100 % for retinal damage, and 0–98 % for globe rupture depending on the blast condition. Orbital geometry affected the stresses, pressures, and associated ocular injury risks of the blast conditions simulated. Orbital geometries that more fully surrounded the eye such as the more protective orbit tended to produce higher corneoscleral stresses and compression of the eye against the surrounding rigid orbit contributing to high stresses as the blast wave propagated. However, the more protective orbit tended to produce lower intra-ocular pressures in comparison with the other three orbital geometries which may indicate that the more protective orbit inhibits propagation of the blast wave and reduces ocular loading. Results of this parametric computational study of ocular blast loading are valuable to the design of eye protection equipment and the mitigation of blast-related eye injuries.     

Occupational Injuries in Germany: Population-Wide National Survey Data Emphasize the Importance of Work-Related Factors

Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18–70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4–3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7–1.2; men: 4.3%; 95% CI 3.7–5.0). In the fully adjusted model, male gender (OR 3.16) and age 18–29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational injuries. While the odds for most work-related factors were as expected, the associations for health-related factors such as smoking, drinking, and chronic diseases were rather weak. In part, this may be due to context-specific factors such as safety and workplace regulations in high-income countries like Germany. This assumption could guide further research, taking a multi-level approach to international comparisons.     

Changes in Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy in a Direct Cranial Blast Traumatic Brain Injury (dc-bTBI) Model

Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1–14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14–19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS.     

Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy?

Mitochondrial dysfunction and oxidative stress contribute to several neurologic disorders and have recently been implicated in acquired epilepsies such as temporal lobe epilepsy (TLE). Acquired epilepsy is typically initiated by a brain injury followed by a "latent period" whereby molecular, biochemical and other cellular alterations occur in the brain leading to chronic epilepsy. Mitochondrial dysfunction and oxidative stress are emerging as factors that not only occur acutely as a result of precipitating injuries such as status epilepticus (SE), but may also contribute to epileptogenesis and chronic epilepsy. Mitochondria are the primary site of reactive oxygen species (ROS) making them uniquely vulnerable to oxidative damage that may affect neuronal excitability and seizure susceptibility. This mini-review provides an overview of evidence suggesting the role of mitochondrial dysfunction and oxidative stress as acute consequences of injuries that are known to incite chronic epilepsy and their involvement in the chronic stages of acquired epilepsy.     

Modelling human eye under blast loading

Primary blast injury (PBI) is the general term that refers to injuries resulting from the mere interaction of a blast wave with the body. Although few instances of primary ocular blast injury, without a concomitant secondary blast injury from debris, are documented, some experimental studies demonstrate its occurrence. In order to investigate PBI to the eye, a finite element model of the human eye using simple constitutive models was developed. The material parameters were calibrated by a multi-objective optimisation performed on available eye impact test data. The behaviour of the human eye and the dynamics of mechanisms occurring under PBI loading conditions were modelled. For the generation of the blast waves, different combinations of explosive (trinitrotoluene) mass charge and distance from the eye were analysed. An interpretation of the resulting pressure, based on the propagation and reflection of the waves inside the eye bulb and orbit, is proposed. The peculiar geometry of the bony orbit (similar to a frustum cone) can induce a resonance cavity effect and generate a pressure standing wave potentially hurtful for eye tissues.     

Examination of the protective roles of helmet/faceshield and directionality for human head under blast waves

A parametric study was conducted to delineate the efficacy of personal protective equipment (PPE), such as ballistic faceshields and advanced combat helmets, in the case of a blast. The propagations of blast waves and their interactions with an unprotected head, a helmeted one, and a fully protected finite element head model (FEHM) were modeled. The biomechanical parameters of the brain were recorded when the FEHM was exposed to shockwaves from the front, back, top, and bottom. The directional dependent tissue response of the brain and the variable efficiency of PPE with respect to the blast orientation were two major results of this study.     

Traumatic brain injury

There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad.     

云南地方稻种持久抗瘟性的研究

1996～1999年,在不同纬度、不同海拔和不同稻作生态类型的重病区设立5个持久抗性稻瘟病鉴定圃.试验材料为云南的74份地方稻种资源,其中粳稻56份,籼稻18份(含野生稻3份).通过多个抗性组分进行了系统研究,初步表明大白谷(粳、墨江县)、毫弄早(籼、勐海县)、毫玉浪(籼、勐海县)、疣粒野生稻(野、西双版纳自治州)等具有持久抗瘟性能;其中疣粒野生稻高抗细菌性条斑病,对白叶枯病抗性为0级,接近免疫,中抗稻瘟病.通过对品种多抗性组分分析和品种抗性系统聚类分析,提出在不同生态类型时、空动态的病叶片上的产孢量和病斑表型可作为简易、快速鉴定持久抗瘟性指标.     

Pulmonary blast injury increases nitric oxide production, disturbs arginine metabolism, and alters the plasma free amino acid pool in rabbits during the early posttraumatic period.

Plasma nitrate + nitrite (nitrates), as final NO products, and free amino acid pool (FAAP) characteristics, as indicators of protein/amino acid metabolism, were analyzed in the early (30 min) period following blast injury. The experiments were performed on 27 rabbits subjected to pulmonary blast injury (experimental group) or not exposed to overpressure (controls). We report that pulmonary blast injury (PBI) induces prompt NO overproduction within a very early period. Increased arginine utilization via NO synthase, presumably associated with its cleavage by arginase, leads to the depletion of the arginine level in arterial plasma 30 min following PBI. Impaired balance between arginine utilization and release/resynthesis from endogenous sources causes disturbed nutritional status and urea cycle activity. Early identification and appropriate management of the changes in amino acid metabolism should be included in the evaluation of patients with blast injury. Furthermore, the results suggest that depleted arterial levels of arginine and NO overproduction may be helpful in diagnosis and prognosis of blast injury.     

Quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer.

Quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhanced the Fenton reaction in phosphate buffer, respectively. The enhancement by quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction may be partly related to their respective actions in the biological systems such as a neurotoxic effect (quinolinic acid), a marked growth-inhibitory action on rice seeding (alpha-picolinic acid and fusaric acid), and an antiseptic (2,6-pyridinedicarboxylic acid). The ultraviolet-visible absorption spectrum of the mixture of alpha-picolinic acid with ferrous ion showed a characteristic visible absorbance band with a lambda(max) at 443 nm, suggesting that alpha-picolinic acid chelate of Fe2+ ion forms in the solution. Similar characteristic visible absorbance band was also observed for the mixture of Fe2+ ion with quinolinic acid (or fusaric acid, or 2,6-pyridinedicarboxylic acid). The chelation seems to be related to the enhancement by quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction. alpha-Picolinic acid was reported to be a toxic substance isolated from the culture liquids of blast mould (Piricularia oryzae CAVARA). On the other hand, it has also been known that chlorogenic acid protects rice plants from the blast disease. The chlorogenic acid inhibited the formation of the hydroxyl radical in the reaction mixture of alpha-picolinic acid, FeSO4(NH4)2SO4, and H2O2. Thus the inhibition may be a possible mechanism of the protective action of the chlorogenic acid against the blast disease.