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24 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Blunt Impact Brain Injury using Cellular Injury Criterion

The Advanced Combat Helmet (\ACH") military specification (\mil-spec") requires a helmeted magnesium (\Mg") Department of Transportation (\DOT") headform be dropped vertically, with an impact speed of 3.1 m/s (10 ft/s), onto a steel hemispherical target. The pass/fail criteria are based on translational acceleration (150 G) alone, absent of any rotational component. Without a rotational component, the specification's injury risk application is limited to skull fracture and peripheral hematomas (subdural, subarachnoid), since this translational acceleration injury risk assessment is based on the Wayne State Tolerance Curve (\WSTC"). To provide a more comprehensive view of injury for the entire brain, an alternative approach is needed. To meet this need, we worked with a larger group called PANTHER, a collaboration between national laboratories, industry, and academia. Collaborations specific to research and results presented here come from efforts led by Mr. Ron Szalkowski and Mr. Sushant Malave, Ms. Alice Fawzi, and Dr. Christian Franck. We have developed a prototypical injury risk criterion based on the neuronal response to abrupt changes in general motion (translation, rotation, or both). The cellular-based mild traumatic brain injury (\cbmTBI") criterion utilizes both the strain and strain rate of brain tissue to account for the stretch and rate of stretch that occurs throughout the brain as a result of blunt impact to the head. We conducted physical experiments of an ACH-fitted magnesium headform, which produced repeatable headform peak accelerations. Then, we developed a simulation of the experiment, and validated the simulation output with the experimental data. We then substituted the magnesium headform with a human headform, consisting of skin, muscle, bone, gray matter, white matter, cerebral-spinal fluid, membranes, vasculature, intravertebral discs, airway and sinus. We quantified brain injury risk using the cbmTBI criterion, using the current mil-spec test and a modified test. The modified mil-spec test used an inclined anvil target that was located posterior to the crown of the helmet in the axial plane. While the current mil-spec test produced brain deformation from head translation alone, the modified test produced brain deformation from head translation and rotation, which is closer to most real world and combat theater impacts (e.g., such as occur in tertiary blast exposure). Compared to the current mil-spec test, the modified test produced elevated strains in the human digital twin. These data, mapped to the cbmTBI criterion, suggest increased injury risk for blunt impacts that cause rotation and translation, rather than just translation alone. Moreover, these data may lead to a rotational performance metric, which is rooted in the biology and pathology of the brain's response to impact and blast, and which should be used to improve next-generation helmet designs.

42 ENGINEERING↗
DOE OSTI2021

Brain-implantable multifunctional probe for simultaneous detection of glutamate and GABA neurotransmitters

We report Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA μM -1 cm -2 and maximum sensitivities of 204 ± 15 nA μM -1 cm -2 and 37 ± 7 nA μM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2 , GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Biofidelic Digital Head Model Software

Researchers at Los Alamos have extensive capabilities in biofidelic modeling, simulation and software development for predicting traumatic brain injury (TBI). Since injury-causing experiments cannot be performed on live humans, and head dummies are incapable of predicting brain deformations/strain, our approach uses magnetic resonance imaging (MRI) data for the brain combined with advanced computational methods and substructure constitutive properties to identify harmful accelerations that may develop diffused axonal injury in the brain. The goal is to develop this capability to analyze the effectiveness of personal protective equipment (PPE) such as, helmets and the advanced energy-absorbing materials used in PPE to mitigate brain injury. Los Alamos is seeking a collaborative partner (through a cooperative research and development agreement) to develop this capability toward a potential technology that will have commercial viability.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2024

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Neurosciences & Neurology↗
DOE OSTI2022

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

The Biomechanics of Indirect Traumatic Optic Neuropathy Using a Computational Head Model With a Biofidelic Orbit

Indirect traumatic optic neuropathy (ITON) is an injury to the optic nerve due to head trauma and usually results in partial or complete loss of vision. In order to advance a mechanistic understanding of the injury to the optic nerve, we developed a head model with a biofidelic orbit. Head impacts were simulated under controlled conditions of impactor velocity. The locations of impact were varied to include frontal, lateral, and posterior parts of the head. Impact studies were conducted using two types of impactors that differed in their rigidity relative to the skull. The simulated results from both the impactors suggest that forehead impacts are those to which the optic nerve is most vulnerable. The mode and location of optic nerve injury is significantly different between the impacting conditions. Simulated results using a relatively rigid impactor (metal cylinder) suggest optic nerve injury initiates at the location of the intracranial end of the optic canal and spreads to the regions of the optic nerve in the vicinity of the optic canal. In this case, the deformation of the skull at the optic canal, resulting in deformation of the optic nerve, was the primary mode of injury. On the other hand, simulated results using a relatively compliant impactor (soccer ball) suggest that primary mode of injury comes from the brain tugging upon the optic nerve (from where it is affixed to the intracranial end of the optic canal) during coup countercoup motion of the brain. This study represents the first published effort to employ a biofidelic simulation of the full length of the optic nerve in which the orbit is integrated within the whole head.

59 BASIC BIOLOGICAL SCIENCES↗