MCC950 Attenuates Microglial NLRP3-Mediated Chronic Neuroinflammation and Memory Impairment in a Rat Model of Repeated Low-Level Blast Exposure.

Blast-induced traumatic brain injury is typically regarded as a signature medical concern for military personnel who are exposed to explosive devices in active combat zones. However, soldiers as well as law enforcement personnel may be repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain neurotrauma from repeated low-level blast (rLLB) exposure do not display overt pathological symptoms immediately but rather develop mild symptoms including cognitive impairments, attention deficits, mood changes, irritability, and sleep disturbances over time.

Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system.

Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model.

Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline's neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity.

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model.

Blast injuries are common among the military service members and veterans. One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss. Treating hearing loss using minocycline is restricted by optimal drug concentration, route of administration, and its half-life.

Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes.

Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness.

Central and peripheral auditory abnormalities in chinchilla animal model of blast-injury.

Exposure to blast overpressure or high-intensity sound can cause injuries to the auditory system, which leads to hearing loss or tinnitus. In this study, we examined the involvement of peripheral auditory system (PAS), and central auditory system (CAS) changes after exposure to blast overpressure (15-25 psi) on Day 1 and additionally during 7 days of post blast time period in chinchillas. Auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and cochlear hair cell changes were measured or identified in post-blast period within 7 days to detect injuries in the PAS.

Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19.

In recent decades, the major concern of emerging and re-emerging viral diseases has become an increasingly important area of public health concern, and it is of significance to anticipate future pandemic that would inevitably threaten human lives. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged virus that causes mild to severe pneumonia. Coronavirus disease (COVID-19) became a very much concerned issue worldwide after its super-spread across the globe and emerging viral diseases have not got specific and reliable diagnostic and treatments.

Does Blast Exposure to the Torso Cause a Blood Surge to the Brain?

The interaction of explosion-induced blast waves with the torso is suspected to contribute to brain injury. In this indirect mechanism, the wave-torso interaction is assumed to generate a blood surge, which ultimately reaches and damages the brain. However, this hypothesis has not been comprehensively and systematically investigated, and the potential role, if any, of the indirect mechanism in causing brain injury remains unclear.

Sensor orientation and other factors which increase the blast overpressure reporting errors.

This study compared the response of the wearable sensors tested against the industry-standard pressure transducers at blast overpressure (BOP) levels typically experienced in training. We systematically evaluated the effects of the sensor orientation with respect to the direction of the incident shock wave and demonstrated how the averaging methods affect the reported pressure values. The evaluated methods included averaging peak overpressure and impulse of all four sensors mounted on a helmet, taking the average of the three sensors, or isolating the incident pressure equivalent using two sensors.

Behavioral Deficits in Animal Models of Blast Traumatic Brain Injury.

Blast exposure has been identified to be the most common cause for traumatic brain injury (TBI) in soldiers. Over the years, rodent models to mimic blast exposures and the behavioral outcomes observed in veterans have been developed extensively. However, blast tube design and varying experimental parameters lead to inconsistencies in the behavioral outcomes reported across research laboratories.

Variations in Constitutive Properties of the Fluid Elicit Divergent Vibrational and Pressure Response Under Shock Wave Loading.

We performed a characterization of the shock wave loading on the response of the specimen representing a simplified head model. A polycarbonate cylinder (2-in. outer diameter, wall thickness: 0.

Blast exposure predisposes the brain to increased neurological deficits in a model of blast plus blunt traumatic brain injury.

Soldiers are often exposed to more than one traumatic brain injury (TBI) over the course of their service. In recent years, more attention has been drawn to the increased risk of neurological deficits caused by the 'blast plus' polytrauma, which typically is a blast trauma combined with other forms of TBI. In this study, we investigated the behavioral and neuronal deficits resulting from a blast plus injury involving a mild-moderate blast followed by a mild blunt trauma using the fluid percussion injury model.

Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury.

The activation of resident microglia and infiltrated monocytes are known potent mediators of chronic neuroinflammation following traumatic brain injury (TBI). In this study, we use a mouse model of blast-induced TBI (bTBI) to investigate whether microglia and monocytes contribute to the neuroinflammatory and behavioral consequences of bTBI. Eight-ten week old mice were subject to moderate TBI (180 kPa) in a shock tube.

Oxidative stress contributes to cerebral metabolomic profile changes in animal model of blast-induced traumatic brain injury.

Introduction: Blast-induced neurotrauma (BINT) has been recognized as the common mode of traumatic brain injury amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from this laboratory have identified three major pathological events following BINT which include blood brain barrier disruption the earliest event, followed by oxidative stress and neuroinflammation as secondary events occurring a few hours following blast.

Objectives: Our recent studies have also identified an increase in oxidative stress mediated by the activation of superoxide producing enzyme NADPH oxidase (NOX) in different brain regions at varying levels with neurons displaying higher oxidative stress (NOX activation) compared to any other neural cell.

The evolution of secondary flow phenomena and their effect on primary shock conditions in shock tubes: Experimentation and numerical model.

Compressed gas-driven shock tubes are widely used for laboratory simulation of primary blasts by accurately replicating pressure profiles measured in live-fire explosions. These investigations require sound characterization of the primary blast wave, including the temporal and spatial evolution of the static and dynamic components of the blast wave. The goal of this work is to characterize the propagation of shock waves in and around the exit of a shock tube via analysis of the primary shock flow, including shock wave propagation and decay of the shock front, and secondary flow phenomena.

A Comprehensive Review of Experimental Rodent Models of Repeated Blast TBI.

We reviewed the relevant literature delineating advances in the development of the experimental models of repeated blast TBI (rbTBI). It appears this subject is a relatively unexplored area considering the first work published in 2007 and the bulk of peer-reviewed papers was published post-2011. There are merely 34 papers published to date utilizing rodent rbTBI models.

Occupational Blast Wave Exposure During Multiday 0.50 Caliber Rifle Course.

Research on blast overpressure (BOP) experienced by military personnel in operations like breaching, identifies transient, measurable effects on operator readiness. Specifically, blast seems to be associated with suppressed response speed and cognitive function. This work evaluates 50 caliber weapon systems to ascertain BOP effects from the weapon usage.

Characterization of a controlled shock wave delivered by a pneumatic table-top gas driven shock tube.

Blast simulators facilitate the creation of shock waves and measurement of pressure morphology in a controlled laboratory setting and are currently a vital model for replicating blast-induced neurotrauma. Due to the maintenance and operation cost of conventional blast simulators, we developed a pneumatic, table-top, gas-driven shock tube to test an alternative method of shock wave generation using a membrane-less driver section. Its unique operational mechanism based on air gun technology does not rely on a plastic membrane rupture for the generation of pressure pulses, allowing the simulator to be quickly reset and thus decreasing the experimental turnaround time.

Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma.

Blast-induced traumatic brain injury (bTBI) has been recognized as the common mode of neurotrauma amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from our laboratory have identified enhanced blood-brain barrier (BBB) permeability as a significant, sub-acute (four hours post-blast) pathological change in bTBI. We also found that NADPH oxidase (NOX)-mediated oxidative stress occurs at the same time post-blast when the BBB permeability changes.

Animal Models of Traumatic Brain Injury and Assessment of Injury Severity.

Traumatic brain injury (TBI) contributes a major cause of death, disability, and mental health disorders. Most TBI patients suffer long-term post-traumatic stress disorder, cognitive dysfunction, and disability. The underlying molecular and cellular mechanisms of such neuropathology progression in TBI remain elusive.

Microglia Receptors in Animal Models of Traumatic Brain Injury.

Microglia have been implicated as a key mediator of chronic inflammation following traumatic brain injury (TBI). The animal models of TBI vary significantly based on the type of brain injury (focal versus diffuse). This has made it extremely difficult to assess the role of microglia and the window of microglia activation.

Effect of Tissue Material Properties in Blast Loading: Coupled Experimentation and Finite Element Simulation.

Computational models of blast-induced traumatic brain injury (bTBI) require a robust definition of the material models of the brain. The mechanical constitutive models of these tissues are difficult to characterize, leading to a wide range of values reported in literature. Therefore, the sensitivity of the intracranial pressure (ICP) and maximum principal strain to variations in the material model of the brain was investigated through a combined computational and experimental approach.

Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury.

Understanding the mechanisms underlying traumatic neural injury and the sequelae of events in the acute phase is important for deciding on the best window of therapeutic intervention. We hypothesized that evoked potentials (EP) recorded from the cerebellar cortex can detect mild levels of neural trauma and provide a qualitative assessment tool for progression of cerebellar injury in time. The cerebellar local field potentials evoked by a mechanical tap on the hand and collected with chronically implanted micro-ECoG arrays on the rat cerebellar cortex demonstrated substantial changes both in amplitude and timing as a result of blast-wave induced injury.