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1.
Acta Bioeng Biomech ; 26(1): 143-151, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-39219074

ABSTRACT

Purpose: The aim of this study is to investigate the dynamic and biomechanical response of the pelvis and thoracolumbar spine in simulated under-body blast (UBB) impacts and design of protective seat cushion for thoracolumbar spine injuries. Methods: A whole-body FE (finite element) human body model in the anthropometry of Chinese 50th% adult male (named as C-HBM) was validated against existing PHMS (Postmortem Human Subjects) test data and employed to understand the dynamic and biomechanical response of the pelvis and thoracolumbar spine from FE simulations of UBB impacts. Then, the protective capability of different seat cushion designs for UBB pelvis and thoracolumbar injury risk was compared based on the predictions of the C-HBM. Results: The predicted spinal accelerations from the C-HUM are almost within the PHMS corridors. UBB impact combined with the effects from physiological curve of the human thoracolumbar spine and torso inertia leads to thoracolumbar spine anterior bending and axial compression, which results in stress concentration in the segments of T4-T8, T12-L1 and L4-L5. Foam seat cushion can effectively reduce the risk of thoracolumbar spine injury of armored vehicle occupants in UBB impacts, and the DO3 foam has better protective performance than ordinary foam, the 60 mm thick DO3 foam could reduce pelvic acceleration peak and DRIz value by 52.8% and 17.2%, respectively. Conclusions: UBB spinal injury risk is sensitive to the input load level, but reducing the pelvic acceleration peak only is not enough for protection of spinal UBB injury risk, control of torso inertia effect would be much helpful.


Subject(s)
Lumbar Vertebrae , Pelvis , Thoracic Vertebrae , Humans , Lumbar Vertebrae/physiopathology , Male , Biomechanical Phenomena , Blast Injuries/prevention & control , Blast Injuries/physiopathology , Adult , Equipment Design , Explosions , Finite Element Analysis , Computer Simulation , Acceleration , Models, Biological , Stress, Mechanical , Protective Devices
2.
Mil Med ; 189(Supplement_3): 291-297, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160868

ABSTRACT

INTRODUCTION: Auditory disabilities like tinnitus and hearing loss caused by exposure to blast overpressures are prevalent among military service members and veterans. The high-pressure fluctuations of blast waves induce hearing loss by injuring the tympanic membrane, ossicular chain, or sensory hair cells in the cochlea. The basilar membrane (BM) and organ of Corti (OC) behavior inside the cochlea during blast remain understudied. A computational finite element (FE) model of the full human ear was used by Bradshaw et al. (2023) to predict the motion of middle and inner ear tissues during blast exposure using a 3-chambered cochlea with Reissner's membrane and the BM. The inclusion of the OC in a blast transmission model would improve the model's anatomy and provide valuable insight into the inner ear response to blast exposure. MATERIALS AND METHODS: This study developed a microscale FE model of the OC, including the OC sensory hair cells, membranes, and structural cells, connected to a macroscale model of the ear to form a comprehensive multiscale model of the human peripheral auditory system. There are 5 rows of hair cells in the model, each row containing 3 outer hair cells (OHCs) and the corresponding Deiters' cells and stereociliary hair bundles. BM displacement 16.75 mm from the base induced by a 31 kPa blast overpressure waveform was derived from the macroscale human ear model reported by Bradshaw et al. (2023) and applied as input to the center of the BM in the OC. The simulation was run for 2 ms as a structural analysis in ANSYS Mechanical. RESULTS: The FE model results reported the displacement and principal strain of the OHCs, reticular lamina, and stereociliary hair bundles during blast transmission. The movement of the BM caused the rest of the OC to deform significantly. The reticular lamina displacement and strain amplitudes were highest where it connected to the OHCs, indicating that injury to this part of the OC may be likely due to blast exposure. CONCLUSIONS: This microscale model is the first FE model of the OC to be connected to a macroscale model of the ear, forming a full multiscale ear model, and used to predict the OC's behavior under blast. Future work with this model will incorporate cochlear endolymphatic fluid, increase the number of OHC rows to 19 in total, and use the results of the model to reliably predict the sensorineural hearing loss resulting from blast exposure.


Subject(s)
Blast Injuries , Computer Simulation , Humans , Blast Injuries/physiopathology , Blast Injuries/complications , Hair Cells, Auditory/physiology , Finite Element Analysis
3.
Mil Med ; 189(Supplement_3): 407-415, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160824

ABSTRACT

INTRODUCTION: Auditory injuries induced by repeated exposures to blasts reduce the operational performance capability and the life quality of military personnel. The treatment for blast-induced progressive hearing damage is lacking. We have recently investigated the therapeutic function of liraglutide, a glucagon-like peptide-1 receptor agonist, to mitigate blast-induced hearing damage in the animal model of chinchilla, under different blast intensities, wearing earplugs (EPs) or not during blasts, and drug-treatment plan. The goal of this study was to investigate the therapeutical function of liraglutide by comparing the results obtained under different conditions. MATERIALS AND METHODS: Previous studies on chinchillas from two under-blast ear conditions (EP/open), two blast plans (G1: 6 blasts at 3-5 psi or G2:3 blasts at 15-25 psi), and three treatment plans (blast control, pre-blast drug treatment, and post-blast drug treatment) were summarized. The auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) recorded within 14 days after the blasts were used. Statistical analysis was performed to evaluate the effect of liraglutide under different conditions. RESULTS: ABR threshold shifts indicated that the conditions of the EP and open ears were substantially different. Results from EP chinchillas indicated that the pre-blast treatment reduced the acute ABR threshold elevation on the day of blasts, and the significance of such an effect increased with the blast level. Liraglutide-treated open chinchillas showed lower ABR threshold shifts at the later stage of the experiment regardless of the blast levels. The DPOAE was less damaged after G2 blasts compared to G1 when pre-blast liraglutide was administrated. Lower post-blast MLR amplitudes were observed in the pre-blast treatment groups. CONCLUSIONS: This study indicated that the liraglutide mitigated the blast-induced auditory injuries. In EP ears, the pre-blast administration of liraglutide reduced the severity of blast-induced acute damage in ears with EP protection, especially under G2. In animals with open ears, the effect of liraglutide on the restoration of hearing increased with time. The liraglutide potentially benefits post-blast hearing through multiple approaches with different mechanics.


Subject(s)
Blast Injuries , Chinchilla , Disease Models, Animal , Liraglutide , Animals , Liraglutide/pharmacology , Liraglutide/therapeutic use , Blast Injuries/complications , Blast Injuries/drug therapy , Blast Injuries/physiopathology , Hearing Loss, Noise-Induced/drug therapy , Hearing Loss, Noise-Induced/physiopathology , Evoked Potentials, Auditory, Brain Stem/drug effects , Evoked Potentials, Auditory, Brain Stem/physiology , Otoacoustic Emissions, Spontaneous/drug effects , Otoacoustic Emissions, Spontaneous/physiology
4.
Mil Med ; 189(Supplement_3): 517-524, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160835

ABSTRACT

INTRODUCTION: With similar prevalence to injuries from fires, stings, and natural disasters, soft tissue injuries may occur from fireworks, industrial accidents, or other explosives. Surgeons are less familiar with treating high-velocity penetration from small debris, which may increase the chance of infection and subsequent fatality. Penetration risk curves have been developed to predict V50, the velocity with 50% probability of penetration, for various sized projectiles. However, there has been limited research using nonmetallic materials to achieve lower density projectiles less than 1 g cm-2, such as sand or rocks. MATERIAL AND METHODS: To emulate the size and density of these energized particles, 14 ball bearings of stainless steel, silicon nitride, or Delrin acetal plastic ranging from 1.59 mm (1/16") to 9.53 mm (3/8") with sectional densities between 0.3 g cm-2 and 5 g cm-2 were launched toward porcine legs at a range of velocities to determine the penetration thresholds. High-speed videography was captured laterally at 40 kHz and impact velocity was captured using a physics-based tracking software. A generalized linear model with repeated measures and a logit link function was used to predict probability of penetration for each projectile. A total of 600 impacts were conducted to achieve at least 15 penetrating impacts for each projectile over a range of velocities. RESULTS: Higher impact velocities were required to penetrate the skin as sectional density of the projectile decreased, and the relationship between velocity and sectional density exhibited an exponential relationship (V50, $ = 184.6*S{D^{ - 0.385}}$, R2 = 0.95) with substantial change for nonlinearity in sectional densities ranging from 0.3 g cm-2 to 1 g cm-2. Compared to previous studies, the empirical relationship was consistent in the linear region (2-5 g cm-2), and novel experimentation filled in the gaps for sectional densities less than 1 g cm-2, which expressed more nonlinearity than previously estimated. For low-density projectiles with diameters of 1.59 (1/16") or 3.18 (1/8"), 32 impacts were lodged into the epidermis but did not penetrate through the dermis; however, penetration was defined as displacement into or through the dermis. CONCLUSIONS: These experimental results may be used to develop and validate finite element simulations of low-density projectile impacts to address complex, multivariate loading conditions for the development of protective clothing to reduce wounding and subsequent infection rates.


Subject(s)
Blast Injuries , Animals , Swine , Blast Injuries/physiopathology , Extremities/injuries
5.
Exp Eye Res ; 247: 110031, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39128668

ABSTRACT

Our previous studies have shown the benefit of intravitreal injection of a mesenchymal stem cell (MSC)- derived secretome to treat visual deficits in a mild traumatic brain injury (mTBI) mouse model. In this study, we have addressed whether MSC-derived extracellular vesicles (EV) overexpressing miR424, which particularly targets neuroinflammation, show similar benefits in the mTBI model. Adult C57BL/6 mice were subjected to a 50-psi air pulse on the left side, overlying the forebrain, resulting in mTBI. Sham-blast mice were controls. Within an hour of blast injury, 3 µl (∼7.5 × 108 particles) of miR424-EVs, native-EVs, or saline was delivered intravitreally. One month later, retinal morphology was observed through optical coherence tomography (OCT); visual function was assessed using optokinetic nystagmus (OKN) and electroretinogram (ERG), followed by immunohistological analysis. A separate study in adult mice tested the dose-response of EVs for safety. Blast injury mice with saline showed decreased visual acuity compared with the sham group (0.30 ± 0.03 vs. 0.39 ± 0.01 c/d, p < 0.02), improved with miR424-EVs (0.39 ± 0.02 c/d, p < 0.01) but not native-EVs (0.33 ± 0.04 c/d, p > 0.05). Contrast sensitivity thresholds of blast mice receiving saline increased compared with the sham group (85.3 ± 5.9 vs. 19.9 ± 4.8, %, p < 0.001), rescued by miR424-EVs (23.6 ± 7.3 %, p < 0.001) and native-EVs (45.6 ± 10.7 %, p < 0.01). Blast injury decreased "b" wave amplitude compared to sham mice (94.6 ± 24.0 vs. 279.2 ± 25.3 µV, p < 0.001), improved with miR424-EVs (173.0 ± 27.2 µV, p < 0.03) and native-EVs (230.2 ± 37.2 µV, p < 0.01) with a similar decrease in a-wave amplitude in blast mice improved with both miR424-EVs and native-EVs. Immunohistology showed increased GFAP and IBA1 in blast mice with saline compared with sham (GFAP: 11.9 ± 1.49 vs. 9.1 ± 0.8, mean intensity/100,000 µm2 area, p < 0.03; IBA1: 36.08 ± 4.3 vs. 24.0 ± 1.54, mean intensity/100,000 µm2 area, p < 0.01), with no changes with native-EVs (GFAP: 12.6 ± 0.79, p > 0.05; IBA1: 32.8 ± 2.9, p > 0.05), and miR424-EV (GFAP: 13.14 ± 0.76, p > 0.05; IBA1: 31.4 ± 2.7, p > 0.05). Both native-EVs and miR424-EVs exhibited vitreous aggregation, as evidenced by particulates in the vitreous by OCT, and increased vascular structures, as evidenced by αSMA and CD31 immunostainings. The number of capillary lumens in the ganglion cell layer increased with increased particles in the eye, with native EVs showing the worst effects. In conclusion, our study highlights the promise of EV-based therapies for treating visual dysfunction caused by mTBI, with miR424-EVs showing particularly strong neuroprotective benefits. Both miR424-EVs and native-EVs provided similar protection, but issues with EV aggregation and astrogliosis or microglial/macrophage activation at the current dosage call for improved delivery methods and dosage adjustments. Future research should investigate the mechanisms behind EVs' effects and optimize miR424 delivery strategies to enhance therapeutic outcomes and reduce complications.


Subject(s)
Blast Injuries , Disease Models, Animal , Electroretinography , Extracellular Vesicles , Mesenchymal Stem Cells , Mice, Inbred C57BL , MicroRNAs , Tomography, Optical Coherence , Animals , Extracellular Vesicles/metabolism , Mice , MicroRNAs/genetics , Blast Injuries/therapy , Blast Injuries/physiopathology , Blast Injuries/metabolism , Blast Injuries/complications , Mesenchymal Stem Cells/metabolism , Male , Nystagmus, Optokinetic/physiology , Intravitreal Injections , Visual Acuity/physiology , Vision Disorders/physiopathology , Vision Disorders/etiology , Vision Disorders/therapy , Mesenchymal Stem Cell Transplantation/methods
6.
Ann Biomed Eng ; 52(10): 2641-2654, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38851659

ABSTRACT

Free-field blast exposure imparts a complex, dynamic response within brain tissue that can trigger a cascade of lasting neurological deficits. Full body mechanical and physiological factors are known to influence the body's adaptation to this seemingly instantaneous insult, making it difficult to accurately pinpoint the brain injury mechanisms. This study examined the intracranial pressure (ICP) profile characteristics in a rat model as a function of blast overpressure magnitude and brain location. Metrics such as peak rate of change of pressure, peak pressure, rise time, and ICP frequency response were found to vary spatially throughout the brain, independent of blast magnitude, emphasizing unique spatial pressure fields as a primary biomechanical component to blast injury. This work discusses the ICP characteristics and considerations for finite element models, in vitro models, and translational in vivo models to improve understanding of biomechanics during primary blast exposure.


Subject(s)
Blast Injuries , Intracranial Pressure , Rats, Sprague-Dawley , Animals , Blast Injuries/physiopathology , Rats , Male , Brain/physiopathology , Brain Injuries/physiopathology , Models, Biological
7.
Vestn Otorinolaringol ; 89(2): 10-14, 2024.
Article in Russian | MEDLINE | ID: mdl-38805457

ABSTRACT

An explosion is a process that rapidly releases a huge amount of energy in the form of heat, kinetic energy, and high-pressure shock waves. Since the organ of hearing is most susceptible to pressure changes, damage to the sound-conducting or sound-receiving systems is inevitable in case of an explosive injury. This article examines the mechanism of formation of explosive injuries of the middle and inner ear in children and adolescents, the features of diagnosis and tactics of surgical reconstructive treatment of explosive ear injuries based on the data available in the scientific literature and their own experience.


Subject(s)
Blast Injuries , Otologic Surgical Procedures , Humans , Blast Injuries/surgery , Blast Injuries/physiopathology , Child , Otologic Surgical Procedures/methods , Otologic Surgical Procedures/adverse effects , Adolescent , Plastic Surgery Procedures/methods , Ear, Middle/surgery , Ear, Middle/injuries , Ear, Middle/physiopathology , Ear, Inner/injuries , Ear, Inner/surgery , Ear, Inner/physiopathology
8.
Med Eng Phys ; 127: 104163, 2024 05.
Article in English | MEDLINE | ID: mdl-38692763

ABSTRACT

Explosions in the battlefield can result in brain damage. Research on the effects of shock waves on brain tissue mainly focuses on the effects of single-orientation blast waves, while there have been few studies on the dynamic response of the human brain to directional explosions in different planes, multi-point explosions and repetitive explosions. Therefore, the brain tissue response and the intracranial pressure (ICP) caused by different blast loadings were numerically simulated using the CONWEP method. In the study of the blast in different directions, the lateral explosion blast wave was found to cause greater ICP than did blasts from other directions. When multi-point explosions occurred in the sagittal plane simultaneously, the ICP in the temporal lobe increased by 37.8 % and the ICP in the parietal lobe decreased by 17.6 %. When multi-point explosions occurred in the horizontal plane, the ICP in the frontal lobe increased by 61.8 % and the ICP in the temporal lobe increased by 12.2 %. In a study of repetitive explosions, the maximum ICP of the second blast increased by 40.6 % over that of the first blast, and that of the third blast increased by 61.2 % over that of the second blast. The ICP on the brain tissue from repetitive blasts can exceed 200 % of that of a single explosion blast wave.


Subject(s)
Blast Injuries , Brain Injuries , Explosions , Intracranial Pressure , Humans , Brain Injuries/physiopathology , Brain Injuries/pathology , Blast Injuries/physiopathology , Blast Injuries/pathology , Brain/physiopathology , Brain/pathology
9.
Stapp Car Crash J ; 67: 44-77, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38662621

ABSTRACT

The goal of this study was to gather and compare kinematic response and injury data on both female and male whole-body Post-mortem Human Surrogates (PMHS) responses to Underbody Blast (UBB) loading. Midsized males (50th percentile, MM) have historically been most used in biomechanical testing and were the focus of the Warrior Injury Assessment Manikin (WIAMan) program, thus this population subgroup was selected to be the baseline for female comparison. Both small female (5th percentile, SF) and large female (75th percentile, LF) PMHS were included in the test series to attempt to discern whether differences between male and female responses were predominantly driven by sex or size. Eleven tests, using 20 whole-body PMHS, were conducted by the research team. Preparation of the rig and execution of the tests took place at the Aberdeen Proving Grounds (APG) in Aberdeen, MD. Two PMHS were used in each test. The Accelerative Loading Fixture (ALF) version 2, located at APG's Bear Point range was used for all male and female whole-body tests in this series. The ALF was an outdoor test rig that was driven by a buried explosive charge, to accelerate a platform holding two symmetrically mounted seats. The platform was designed as a large, rigid frame with a deformable center section that could be tuned to simulate the floor deformation of a vehicle during a UBB event. PMHS were restrained with a 5-point harness, common in military vehicle seats. Six-degree-of-freedom motion blocks were fixed to L3, the sacrum, and the left and right iliac wings. A three-degree-of freedom block was fixed to T12. Strain gages were placed on L4 and multiple locations on the pelvis. Accelerometers on the floor and seat of the ALF provided input data for each PMHS' feet and pelvis. Time histories and mean peak responses in z-axis acceleration were similar among the three PMHS groups in this body region. Injury outcomes were different and seemed to be influenced by both sex and size contributions. Small females incurred pelvis injuries in absence of lumbar injures. Midsized males had lumbar vertebral body fractures without pelvis injuries. And large females with injuries had both pelvis and lumbar VB fractures. This study provides evidence supporting the need for female biomechanical testing to generate female response and injury thresholds. Without the inclusion of female PMHS, the differences in the injury patterns between the small female and midsized male groups would not have been recognized. Standard scaling methods assume equivalent injury patterns between the experimental and scaled data. In this study, small female damage occurred in a different anatomical structure than for the midsized males. This is an important discovery for the development of anthropomorphic test devices, injury criteria, and injury mitigating technologies. The clear separation of small female damage results, in combination with seat speeds, suggest that the small female pelvis injury threshold in UBB events lies between 4 - 5 m/s seat speed. No inference can be made about the small female lumbar threshold, other than it is likely at higher speeds and/or over longer duration. Male lumbar spine damage occurred in both the higher- and lower lower-rate tests, indicating the injury threshold would be below the seat pulses tested in these experiments. Large females exhibited injury patterns that reflected both the small female and midsized male groups - with damaged PMHS having fractures in both pelvis and lumbar, and in both higher- and lower- rate tests. The difference in damage patterns between the sex and size groups should be considered in the development of injury mitigation strategies to protect across the full population.


Subject(s)
Blast Injuries , Cadaver , Explosions , Lumbar Vertebrae , Humans , Male , Female , Blast Injuries/physiopathology , Biomechanical Phenomena , Lumbar Vertebrae/injuries , Middle Aged , Adult , Pelvis/injuries , Aged , Manikins , Sex Factors
10.
Mil Med ; 189(9-10): e2069-e2077, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38553989

ABSTRACT

INTRODUCTION: Cumulative low-level blast exposure during military training may be a significant occupational hazard, increasing the risk of poor long-term outcomes in brain function. US Public Law 116-92 section 717 mandates that US Department of Defense agencies document the blast exposure of each Service member to help inform later disability and health care decisions. However, which empirical measures of training blast exposure, such as the number of incidents, peak overpressure, or impulse, best inform changes in the neurobehavioral symptoms reflecting brain health have not been established. MATERIALS AND METHODS: This study was approved by the US Army Special Operations Command, the University of North Carolina at Chapel Hill, and the VA Puget Sound Health Care System. Using methods easily deployable across different organizational structures, this study sought to identify and measure candidate risk factors related to career occupational blast exposure predictive of changes in neurobehavioral symptom burden. Blast dosimetry-symptom relationships were first evaluated in mice and then tested in a military training environment. In mice, the righting time neurobehavioral response was measured after exposure to a repetitive low-level blast paradigm modeled after Special Operations training. In the military training environment, 23 trainees enrolled in a 6-week explosive breaching training course, 13 instructors, and 10 Service member controls without blast exposure participated in the study (46 total). All participants provided weekly Neurobehavioral Symptom Inventory (NSI) surveys. Peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service were analyzed by Bayesian analysis of regression modeling to determine their probability of influence on the post-training symptoms reported by participants. RESULTS: We tested the hypothesis that cumulative measures of low-level blast exposure were predictive of changes in neurobehavioral symptoms. In mice, repetitive blast resulted in reduced righting times correlated with cumulative blast impulse. In Service members, peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service all showed strong evidence of influence on NSI scores after blast exposure. However, only models including baseline NSI scores and cumulative blast impulse provided significant predictive value following validation. CONCLUSIONS: These results indicate that measures of cumulative blast impulse may have utility in predicting changes in NSI scores. Such paired dosimetry-symptom measures are expected to be an important tool in safely guiding Service members' occupational exposure and optimizing force readiness and lethality.


Subject(s)
Blast Injuries , Military Personnel , Blast Injuries/psychology , Blast Injuries/complications , Blast Injuries/physiopathology , Humans , Animals , Mice , Military Personnel/statistics & numerical data , Military Personnel/psychology , Male , Bayes Theorem , Occupational Exposure/adverse effects , Occupational Exposure/statistics & numerical data , Female , Behavioral Symptoms/etiology , Behavioral Symptoms/diagnosis
11.
Mil Med ; 189(9-10): e1938-e1946, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38401164

ABSTRACT

INTRODUCTION: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. MATERIAL AND METHODS: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. RESULTS: After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. CONCLUSIONS: In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.


Subject(s)
Brain Concussion , Magnetic Resonance Imaging , Humans , Male , Adult , Female , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Brain Concussion/physiopathology , Cohort Studies , Blast Injuries/complications , Blast Injuries/diagnostic imaging , Blast Injuries/physiopathology , Veterans/statistics & numerical data , Middle Aged
12.
J Trace Elem Med Biol ; 78: 127189, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37201369

ABSTRACT

BACKGROUND: In connection with the widespread use of explosive devices in military conflicts, in particular in Ukraine, is relevant to detect the biometals changes in the cerebellum and determine the presence of their influence on the behavior changes of rats in the elevated plus maze in the acute period of a mild blast-traumatic brain injury (bTBI). METHODS: The selected rats were randomly divided into 3 groups: Group I - Experimental with bTBI (with an excess pressure of 26-36 kPa), Group II - Sham and Group III - Intact. Behavior studies was in the elevated plus maze. Brain spectral analysis was with using of energy dispersive X-ray fluorescence analysis, after obtaining the quantitative mass fractions of biometals, the ratios of Cu/Fe, Cu/Zn, Zn/Fe were calculated and the data between the three groups were compared. RESULTS: The results showed an increase in mobility in the experimental rats, which indicates functional disorders of the cerebellum in the form of maladaptation in space. Changes in cognitive activity also is an evidence of cerebellum suppression, which is indicated by changes in vertical locomotor activity. Grooming time was shortened. We established a significant increase in Cu/Fe and Zn/Fe ratios in the cerebellum, a decrease in Cu/Zn. CONCLUSIONS: Changes in the Cu/Fe, Cu/Zn, and Zn/Fe ratios in the cerebellum correlate with impaired locomotor and cognitive activity in rats in the acute posttraumatic period. Accumulation of Fe on the 1st and 3rd day leads to disturbance of the Cu and Zn balance on the 7th day and starts a "vicious cycle" of neuronal damage. Cu/Fe, Cu/Zn, and Zn/Fe imbalances are secondary factors in the pathogenesis of brain damage as a result of primary bTBI.


Subject(s)
Blast Injuries , Brain Injuries , Cerebellum , Copper , Iron , Trace Elements , Zinc , Trace Elements/analysis , Trace Elements/metabolism , Animals , Rats , Brain Injuries/metabolism , Brain Injuries/physiopathology , Blast Injuries/metabolism , Blast Injuries/physiopathology , Cerebellum/chemistry , Cerebellum/metabolism , Cerebellum/physiopathology , Male , Rats, Wistar , Copper/analysis , Copper/metabolism , Iron/analysis , Iron/metabolism , Zinc/analysis , Zinc/metabolism , Grooming , Locomotion , Spectrometry, X-Ray Emission
13.
Fluids Barriers CNS ; 19(1): 5, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-35012589

ABSTRACT

BACKGROUND: Altered cerebrovascular function and accumulation of amyloid-ß (Aß) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer's disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Aß on cellular components of the NVU and capillary network are not well understood. METHODS: We exposed young adult (age range: 76-106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Aß amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Aß load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRß-immunoreactive pericytes, and capillary densities in both genotypes. RESULTS: The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes. CONCLUSION: In conditions of high brain concentrations of human Aß, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides/metabolism , Blast Injuries , Brain Injuries, Traumatic , Microvessels , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Animals , Blast Injuries/complications , Blast Injuries/metabolism , Blast Injuries/physiopathology , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/physiopathology , Disease Models, Animal , Female , Humans , Mice , Mice, Transgenic , Microvessels/metabolism , Microvessels/physiopathology
14.
Br J Anaesth ; 128(2): e127-e134, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34774294

ABSTRACT

Injury scoring systems can be used for triaging, predicting morbidity and mortality, and prognosis in mass casualty incidents. Recent conflicts and civilian incidents have highlighted the unique nature of blast injuries, exposing deficiencies in current scoring systems. Here, we classify and describe deficiencies with current systems used for blast injury. Although current scoring systems highlight survival trends for populations, there are several major limitations. The reliable prediction of mortality on an individual basis is inaccurate. Other limitations include the saturation effect (where scoring systems are unable to discriminate between high injury score individuals), the effect of the overall injury burden, lack of precision in discriminating between mechanisms of injury, and a lack of data underpinning scoring system coefficients. Other factors influence outcomes, including the level of healthcare and the delay between injury and presentation. We recommend that a new score incorporates the severity of injuries with the mechanism of blast injury. This may include refined or additional codes, severity scores, or both, being added to the Abbreviated Injury Scale for high-frequency, blast-specific injuries; weighting for body regions associated with a higher risk for death; and blast-specific trauma coefficients. Finally, the saturation effect (maximum value) should be removed, which would enable the classification of more severe constellations of injury. An early accurate assessment of blast injury may improve management of mass casualty incidents.


Subject(s)
Blast Injuries/physiopathology , Injury Severity Score , Mass Casualty Incidents , Blast Injuries/classification , Blast Injuries/mortality , Delivery of Health Care/organization & administration , Humans , Prognosis , Time Factors , Triage/methods
15.
J Neurophysiol ; 126(4): 1172-1189, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34469703

ABSTRACT

Blast-induced hearing difficulties affect thousands of veterans and civilians. The long-term impact of even a mild blast exposure on the central auditory system is hypothesized to contribute to lasting behavioral complaints associated with mild blast traumatic brain injury (bTBI). Although recovery from mild blast has been studied separately over brief or long time windows, few, if any, studies have investigated recovery longitudinally over short-term and longer-term (months) time windows. Specifically, many peripheral measures of auditory function either recover or exhibit subclinical deficits, masking deficits in processing complex, real-world stimuli that may recover differently. Thus, examining the acute time course and pattern of neurophysiological impairment using appropriate stimuli is critical to better understanding and intervening in bTBI-induced auditory system impairments. Here, we compared auditory brainstem response, middle-latency auditory-evoked potentials, and envelope following responses. Stimuli were clicks, tone pips, amplitude-modulated tones in quiet and in noise, and speech-like stimuli (iterated rippled noise pitch contours) in adult male rats subjected to mild blast and sham exposure over the course of 2 mo. We found that blast animals demonstrated drastic threshold increases and auditory transmission deficits immediately after blast exposure, followed by substantial recovery during the window of 7-14 days postblast, although with some deficits remaining even after 2 mo. Challenging conditions and speech-like stimuli can better elucidate mild bTBI-induced auditory deficit during this period. Our results suggest multiphasic recovery and therefore potentially different time windows for treatment, and deficits can be best observed using a small battery of sound stimuli.NEW & NOTEWORTHY Few studies on blast-induced hearing deficits go beyond simple sounds and sparsely track postexposure. Therefore, the recovery arc for potential therapies and real-world listening is poorly understood. Evidence suggested multiple recovery phases over 2 mo postexposure. Hearing thresholds largely recovered within 14 days and partially explained recovery. However, midlatency responses, responses to amplitude modulation in noise, and speech-like pitch sweeps exhibited extended changes, implying persistent central auditory deficits and the importance of subclinical threshold shifts.


Subject(s)
Auditory Perception/physiology , Auditory Threshold/physiology , Blast Injuries/physiopathology , Brain Concussion/physiopathology , Evoked Potentials, Auditory/physiology , Hearing Disorders/physiopathology , Recovery of Function/physiology , Acoustic Stimulation , Animals , Behavior, Animal/physiology , Blast Injuries/complications , Brain Concussion/etiology , Disease Models, Animal , Electroencephalography , Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Disorders/etiology , Male , Pitch Perception/physiology , Rats
16.
Brain Res ; 1767: 147541, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34077763

ABSTRACT

Matrix metalloproteinase 2 (MMP2) is a gelatinase with multiple functions at the neurovascular interface, including local modification of the glia limitans to facilitate access of immune cells into the brain and amyloid-beta degradation during responses to injury or disease. This study examines regional changes in immunoreactive MMP2 in the rat brain after a single mild (2.7-7.9 psi peak) or moderate (13-17.5 psi peak) blast overpressure (BOP) exposure. Immunopositive MMP2 expression was examined quantitatively in histological sections of decalcified rat heads as a marker at 2, 24, and 72 h after BOP. The MMP2 immunoreactivity was isolated to patchy deposits in brain parenchyma surrounding blood vessels. Separate analyses were conducted for the cerebellum, brain stem caudal to the thalamo-mesencephalic junction, and the cerebrum (including diencephalon). The deposits varied in number, size, staining homogeneity (standard deviation of immunopositive region), and a cumulative measure, the product of size, average intensity and number, as a function of blast intensity and time. The sequences of changes in MMP2 spots from sham control animals suggested that the mild BOP exposure differences normalized within 72 h. However, the responses to moderate exposure revealed a delayed response at 72 h in the subtentorial brain stem and the cerebrum, but not the cerebellum. Hence, local MMP2 responses may be a contextual biomarker for locally regulated responses to widely distributed brain injury foci.


Subject(s)
Blast Injuries/physiopathology , Brain Injuries, Traumatic/physiopathology , Matrix Metalloproteinase 2/metabolism , Animals , Disease Models, Animal , Female , Matrix Metalloproteinase 2/physiology , Rats , Rats, Sprague-Dawley
17.
Oxid Med Cell Longev ; 2021: 8899274, 2021.
Article in English | MEDLINE | ID: mdl-34007409

ABSTRACT

Previous studies found that blast injury caused a significant increased expression of interleukin-1, IL-6, and tumor necrosis factor, a significant decrease in the expression of IL-10, an increase in Evans blue leakage, and a significant increase in inflammatory cell infiltration in the lungs. However, the molecular characteristics of lung injury at different time points after blast exposure have not yet been reported. Therefore, in this study, tandem mass spectrometry (TMT) quantitative proteomics and bioinformatics analysis were used for the first time to gain a deeper understanding of the molecular mechanism of lung blast injury at different time points. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h, and 1 w after low-intensity blast exposure. TMT quantitative proteomics and bioinformatics analysis were performed to analyze protein expression profiling in the lungs from control and blast-exposed mice, and differential protein expression was verified by Western blotting. The results demonstrated that blast exposure induced severe lung injury, leukocyte infiltration, and the production of inflammatory factors in mice. After analyzing the expression changes in global proteins and inflammation-related proteomes after blast exposure, the results showed that a total of 6861 global proteins and 608 differentially expressed proteins were identified, of which 215, 128, 187, 232, and 65 proteins were identified at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. Moreover, blast exposure-induced 177 differentially expressed proteins were associated with inflammatory responses, which were enriched in the inflammatory response regulation, leukocyte transendothelial migration, phagocytosis, and immune response. Therefore, blast exposure may induce early inflammatory response of lung tissue by regulating the expression of key proteins in the inflammatory process, suggesting that early inflammatory response may be the initiating factor of lung blast injury. These data can provide potential therapeutic candidates or approaches for the development of future treatment of lung blast injury.


Subject(s)
Blast Injuries/physiopathology , Inflammation/physiopathology , Leukocytes/metabolism , Lung Injury/physiopathology , Phagocytosis/physiology , Proteomics/methods , Transendothelial and Transepithelial Migration/physiology , Animals , Disease Models, Animal , Male , Mice
18.
Retina ; 41(12): 2564-2570, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34050100

ABSTRACT

BACKGROUND/PURPOSE: To characterize the nature of posterior segment ocular injuries in combat trauma. METHODS: Eyes in the Walter Reed Ocular Trauma Database were evaluated for the presence of posterior segment injury. Final visual outcomes in open-globe versus closed-globe injuries and by zone of injury and the types of posterior segment injuries in open-globe versus closed-globe injuries were assessed. RESULTS: Four hundred fifty-two of 890 eyes (50.8%) had at least one posterior segment injury. The mechanism of injury was most commonly an improvised explosive device in 280 (62.0%) eyes. Sixty-one patients (13.5%) had a Zone I injury, 50 (11.1%) a Zone II injury, and 341 (75.4%) a Zone III injury. Patients with Zone I injuries were more likely to have a final visual acuity of 20/200 or better compared with patients with either a Zone II (P < 0.001) or Zone III injury (P = 0.007). Eyes with a closed-globe injury were more likely to have a final visual acuity of 20/200 or better compared with those with an open-globe injury (P < 0.001). Furthermore, closed-globe injury compared with open-globe injury had a lower risk of vitreous hemorrhage (odds ratio 0.32, P < 0.001), proliferative vitreoretinopathy (odds ratio 0.14, P < 0.001), and retinal detachment (odds ratio 0.18, P < 0.001) but a higher risk of chorioretinal rupture (odds ratio 2.82, P < 0.001) and macular hole (odds ratio 3.46, P = 0.004). CONCLUSION: Patients with combat ophthalmic trauma had similar posterior segment injury patterns to civilian trauma in open-globe versus closed-globe injuries. Zone II and III injuries were associated with a worse visual prognosis.


Subject(s)
Blast Injuries/epidemiology , Eye Injuries, Penetrating/epidemiology , Posterior Eye Segment/injuries , War-Related Injuries/epidemiology , Wounds, Nonpenetrating/epidemiology , Adolescent , Adult , Blast Injuries/physiopathology , Blast Injuries/surgery , Eye Injuries, Penetrating/physiopathology , Eye Injuries, Penetrating/surgery , Female , Humans , Iraq War, 2003-2011 , Male , Middle Aged , Military Medicine , Military Personnel , Posterior Eye Segment/physiopathology , Retrospective Studies , Trauma Severity Indices , Visual Acuity/physiology , War-Related Injuries/physiopathology , War-Related Injuries/surgery , Wounds, Nonpenetrating/physiopathology , Wounds, Nonpenetrating/surgery , Young Adult
19.
Comput Math Methods Med ; 2021: 6638724, 2021.
Article in English | MEDLINE | ID: mdl-33927783

ABSTRACT

Mild, blast-induced traumatic brain injury (mbTBI) is a common combat brain injury characterized by typically normal neuroimaging findings, with unpredictable future cognitive recovery. Traditional methods of electroencephalography (EEG) analysis (e.g., spectral analysis) have not been successful in detecting the degree of cognitive and functional impairment in mbTBI. We therefore collected resting state EEG (5 minutes, 64 leads) from twelve patients with a history of mbTBI, along with repeat neuropsychological testing (D-KEFS Tower test) to compare two new methods for analyzing EEG (multifractal detrended fluctuation analysis (MF-DFA) and information transfer modeling (ITM)) with spectral analysis. For MF-DFA, we extracted relevant parameters from the resultant multifractal spectrum from all leads and compared with traditional power by frequency band for spectral analysis. For ITM, because the number of parameters from each lead far exceeded the number of subjects, we utilized a reduced set of 10 leads which were compared with spectral analysis. We utilized separate 30 second EEG segments for training and testing statistical models based upon regression tree analysis. ITM and MF-DFA models both generally had improved accuracy at correlating with relevant measures of cognitive performance as compared to spectral analytic models ITM and MF-DFA both merit additional research as analytic tools for EEG and cognition in TBI.


Subject(s)
Blast Injuries/diagnosis , Blast Injuries/physiopathology , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/physiopathology , Electroencephalography/statistics & numerical data , Adult , Blast Injuries/psychology , Brain Injuries, Traumatic/psychology , Cognition/physiology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Computational Biology , Executive Function/physiology , Female , Fourier Analysis , Fractals , Humans , Male , Models, Neurological , Models, Psychological , Neuropsychological Tests , Regression Analysis , Software
20.
Neuropsychology ; 35(3): 241-251, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33829824

ABSTRACT

OBJECTIVE: To evaluate the relationships among performance validity, symptom validity, symptom self-report, and objective cognitive testing. METHOD: Combat Veterans (N = 338) completed a neurocognitive assessment battery and several self-report symptom measures assessing depression, posttraumatic stress disorder (PTSD) symptoms, sleep quality, pain interference, and neurobehavioral complaints. All participants also completed two performance validity tests (PVTs) and one stand-alone symptom validity test (SVT) along with two embedded SVTs. RESULTS: Results of an exploratory factor analysis revealed a three-factor solution: performance validity, cognitive performance, and symptom report (SVTs loaded on the third factor). Results of t tests demonstrated that participants who failed PVTs displayed significantly more severe symptoms and significantly worse performance on most measures of neurocognitive functioning compared to those who passed. Participants who failed a stand-alone SVT also reported significantly more severe symptomatology on all symptom report measures, but the pattern of cognitive performance differed based on the selected SVT cutoff. Multiple linear regressions revealed that both SVT and PVT failure explained unique variance in symptom report, but only PVT failure significantly predicted cognitive performance. CONCLUSIONS: Performance and symptom validity tests measure distinct but related constructs. SVTs and PVTs are significantly related to both cognitive performance and symptom report; however, the relationship between symptom validity and symptom report is strongest. SVTs are also differentially related to cognitive performance and symptom report based on the utilized cutoff score. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Blast Injuries/psychology , Brain Injuries, Traumatic/psychology , Malingering/diagnosis , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology , Adult , Aged , Blast Injuries/physiopathology , Brain Injuries, Traumatic/physiopathology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Reproducibility of Results , Self Report , Young Adult
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