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International Journal of Molecular... Jan 2024Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that... (Review)
Review
Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.
Topics: Animals; Humans; Blast Injuries; Endothelial Cells; Brain Concussion; Vascular System Injuries; Astrocytes; Inflammation
PubMed: 38256223
DOI: 10.3390/ijms25021150 -
British Journal of Anaesthesia Aug 2014Trauma is the leading cause of death during the first four decades of life in the developed countries. Its haemodynamic response underpins the patient's initial ability... (Review)
Review
Trauma is the leading cause of death during the first four decades of life in the developed countries. Its haemodynamic response underpins the patient's initial ability to survive, and the response to treatment and subsequent morbidity and resolution. Trauma causes a number of insults including haemorrhage, tissue injury (nociception) and, predominantly, in military casualties, blast from explosions. This article discusses aspects of the haemodynamic responses to these insults and subsequent treatment. 'Simple' haemorrhage (blood loss without significant volume of tissue damage) causes a biphasic response: mean arterial blood pressure (MBP) is initially maintained by the baroreflex (tachycardia and increased vascular resistance, Phase 1), followed by a sudden decrease in MAP initiated by a second reflex (decrease in vascular resistance and bradycardia, Phase 2). Phase 2 may be protective. The response to tissue injury attenuates Phase 2 and may cause a deleterious haemodynamic redistribution that compromises blood flow to some vital organs. In contrast, thoracic blast exposure augments Phase 2 of the response to haemorrhage. However, hypoxaemia from lung injury limits the effectiveness of hypotensive resuscitation by augmenting the attendant shock state. An alternative strategy ('hybrid resuscitation') whereby tissue perfusion is increased after the first hour of hypotensive resuscitation by adopting a revised normotensive target may ameliorate these problems. Finally, morphine also attenuates Phase 2 of the response to haemorrhage in some, but not all, species and this is associated with poor outcome. The impact on human patients is currently unknown and is the subject of a current physiological investigation.
Topics: Analgesics, Opioid; Blast Injuries; Healthy Volunteers; Hemodynamics; Hemorrhage; Humans; Musculoskeletal System; Oxygen Consumption; Resuscitation; Wounds and Injuries
PubMed: 25038158
DOI: 10.1093/bja/aeu232 -
Philosophical Transactions of the Royal... Jan 2011Lung injuries, predominantly arising from blast exposure, are a clinical problem in a significant minority of current military casualties. This special feature consists... (Review)
Review
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.
Topics: Blast Injuries; Bombs; Humans; Military Medicine; Respiratory Distress Syndrome; Warfare
PubMed: 21149364
DOI: 10.1098/rstb.2010.0249 -
Journal of the Royal Army Medical Corps Feb 2019
Topics: Blast Injuries; Humans; Interdisciplinary Research; Military Medicine; Quality Improvement
PubMed: 29769370
DOI: 10.1136/jramc-2018-000968 -
Journal of Neurotrauma Sep 2017Blast-related traumatic brain injury (TBI) is a signature injury of recent military conflicts, leading to increased Department of Defense (DoD) interest in its potential...
Blast-related traumatic brain injury (TBI) is a signature injury of recent military conflicts, leading to increased Department of Defense (DoD) interest in its potential long-term effects, such as chronic traumatic encephalopathy (CTE). The DoD Blast Injury Research Program Coordinating Office convened the 2015 International State-of-the-Science Meeting to discuss the existing evidence regarding a causal relationship between TBI and CTE. Over the course of the meeting, experts across government, academia, and the sports community presented cutting edge research on the unique pathological characteristics of blast-related TBI, blast-related neurodegenerative mechanisms, risk factors for CTE, potential biomarkers for CTE, and treatment strategies for chronic neurodegeneration. The current paper summarizes these presentations. Although many advances have been made to address these topics, more research is needed to establish the existence of links between the long-term effects of single or multiple blast-related TBI and CTE.
Topics: Blast Injuries; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Humans; Military Medicine; Warfare
PubMed: 28937955
DOI: 10.1089/neu.2017.5220 -
The Journal of Head Trauma...To examine global disability trajectories in US military with and without traumatic brain injury (TBI) over the first decade following deployment to identify risk... (Observational Study)
Observational Study
OBJECTIVE
To examine global disability trajectories in US military with and without traumatic brain injury (TBI) over the first decade following deployment to identify risk profiles for better intervention stratification, hopefully reducing long-term cost.
SETTING
Patients and participants were enrolled in combat or directly following medical evacuation at the time of injury and followed up every 6 months for 10 years.
PARTICIPANTS
There are 4 main groups (n = 475), 2 primary and 2 exploratory: (1) combat-deployed controls without a history of blast exposure "non-blast- control" (n = 143), (2) concussive blast TBI "'blast-TBI" (n = 236) (primary), (3) combat-deployed controls with a history of blast exposure "blast-control" (n = 54), and (4) patients sustaining a combat concussion not from blast "non-blast-TBI" (n = 42) (exploratory).
DESIGN
Prospective, observational, longitudinal study.
MAIN MEASURES
Combat concussion, blast exposure, and subsequent head injury exposure over the first decade post-deployment. Global disability measured by the Glasgow Outcome Scale Extended (GOSE).
RESULTS
Latent class growth analysis identified 4 main trajectories of global outcome, with service members sustaining combat concussion 37 to 49 times more likely to be in the worse disability trajectories than non-blast-controls (blast-TBI: odds ratio [OR] = 49.33; CI, 19.77-123.11; P < .001; non-blast-TBI: OR = 37.50; CI, 10.01-140.50; P < .001). Even blast-exposed-controls were 5 times more likely to be in these worse disability categories compared with non-blast-controls (OR = 5.00; CI, 1.59-15.99; P = .007). Adjustment for demographic factors and subsequent head injury exposure did not substantially alter these odds ratios.
CONCLUSIONS
Very high odds of poor long-term outcome trajectory were identified for those who sustained a concussion in combat, were younger at the time of injury, had lower education, and enlisted in the Army above the risk of deployment alone. These findings help identify a risk profile that could be used to target early intervention and screen for poor long-term outcome to aid in reducing the high public health cost and enhance the long-term quality of life for these service members following deployment.
Topics: Blast Injuries; Brain Concussion; Brain Injuries, Traumatic; Craniocerebral Trauma; Humans; Longitudinal Studies; Military Personnel; Prospective Studies; Quality of Life; Stress Disorders, Post-Traumatic
PubMed: 35258037
DOI: 10.1097/HTR.0000000000000738 -
British Journal of Anaesthesia Feb 2022In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic...
BACKGROUND
In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic shock is common after mass casualty incidents. We hypothesised that pre-hospital CPAP is also beneficial after PBLI accompanied by haemorrhagic shock.
METHODS
We performed a computer-based simulation of the cardiopulmonary response to PBLI followed by haemorrhage, calibrated from published controlled porcine experiments exploring blast injury and haemorrhagic shock. The effect of different CPAP levels was simulated in three in silico patients who had sustained mild, moderate, or severe PBLI (10%, 25%, 50% contusion of the total lung) plus haemorrhagic shock. The primary outcome was arterial partial pressure of oxygen (Pao) at the end of each simulation.
RESULTS
In mild blast lung injury, 5 cm HO ambient-air CPAP increased Pao from 10.6 to 12.6 kPa. Higher CPAP did not further improve Pao. In moderate blast lung injury, 10 cm HO CPAP produced a larger increase in Pao (from 8.5 to 11.1 kPa), but 15 cm HO CPAP produced no further benefit. In severe blast lung injury, 5 cm HO CPAP inceased Pao from 4.06 to 8.39 kPa. Further increasing CPAP to 10-15 cm HO reduced Pao (7.99 and 7.90 kPa, respectively) as a result of haemodynamic impairment resulting from increased intrathoracic pressures.
CONCLUSIONS
Our modelling study suggests that ambient air 5 cm HO CPAP may benefit casualties suffering from blast lung injury, even with severe haemorrhagic shock. However, higher CPAP levels beyond 10 cm HO after severe lung injury reduced oxygen delivery as a result of haemodynamic impairment.
Topics: Animals; Blast Injuries; Computer Simulation; Continuous Positive Airway Pressure; Emergency Medical Services; Humans; Lung Injury; Male; Mass Casualty Incidents; Oxygen; Partial Pressure; Pulmonary Gas Exchange; Respiratory Insufficiency; Severity of Illness Index; Shock; Swine; Young Adult
PubMed: 34863511
DOI: 10.1016/j.bja.2021.10.012 -
International Journal of Molecular... Aug 2020Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of... (Review)
Review
Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1β, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI.
Topics: Alarmins; Animals; Blast Injuries; Humans; Lung Injury; Signal Transduction
PubMed: 32878118
DOI: 10.3390/ijms21176303 -
Journal of the Royal Army Medical Corps Dec 2009Since World War II, more vehicles have been lost to land mines than all other threats combined. Anti-vehicular (AV) mines are capable of disabling a heavy vehicle, or... (Review)
Review
Since World War II, more vehicles have been lost to land mines than all other threats combined. 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-offnature 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 operating in Iraq and Afghanistan. Detonation of an AV mine causes an explosive, exothermic reaction which results in the formation of a shockwave followed by a rapid expansion of gases. The shockwave is mainly reflected by the soillair interface and fractures the soil cap overthe mine. The detonation products then vent through the voids in the soil, resulting in a hollow inverse cone which consists of the detonation gases surrounded by the soil ejecta. It is the combination of the detonation products and soil ejecta that interact with the target vehicle and cause injury to the vehicle occupants. 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.
Topics: Afghan Campaign 2001-; Afghanistan; Automobiles; Blast Injuries; Bombs; Explosive Agents; Humans; Iraq; Iraq War, 2003-2011; Military Medicine; Off-Road Motor Vehicles; Physics; United Kingdom
PubMed: 20397600
DOI: 10.1136/jramc-155-04-06 -
Singapore Medical Journal Jan 2009Bomb blast injuries are no longer confined to battlefields. With the ever present threat of terrorism, we should always be prepared for bomb blasts. Bomb blast injuries... (Review)
Review
Bomb blast injuries are no longer confined to battlefields. With the ever present threat of terrorism, we should always be prepared for bomb blasts. Bomb blast injuries tend to affect air-containing organs more, as the blast wave tends to exert a shearing force on air-tissue interfaces. Commonly-injured organs include the tympanic membranes, the sinuses, the lungs and the bowel. Of these, blast lung injury is the most challenging to treat. The clinical picture is a mix of acute respiratory distress syndrome and air embolism, and the institution of positive pressure ventilation in the presence of low venous pressures could cause systemic arterial air embolism. The presence of a tympanic membrane perforation is not a reliable indicator of the presence of a blast injury in the other air-containing organs elsewhere. Radiological imaging of the head, chest and abdomen help with the early identification of blast lung injury, head injury, abdominal injury, eye and sinus injuries, as well as any penetration by foreign bodies. In addition, it must be borne in mind that bomb blasts could also be used to disperse radiological and chemical agents.
Topics: Blast Injuries; Bombs; Diagnostic Imaging; Humans; Mass Casualty Incidents; Terrorism; Triage
PubMed: 19224092
DOI: No ID Found