Modeling biomarker kinetics of Aβ levels in serum following blast

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Апрель 4, 2025

Elucidating the unique neuropathological response to blast exposure remains a barrier towards development of diagnostic approaches for those with blast-induced traumatic brain injury (bTBI). Quantification biomarker concentrations in blood post-injury is typically used inform severity. However, progression and associated changes are sensitive parameters such as overpressure (BOP) magnitude frequency exposure. Through this work, blast-dose kinetics (BxK) platform was developed validated Aβ42 promising predictor post-blast. Blast-dose responses accounting BOP were integrated into mathematical model whole-body Aβ peptide kinetics. Validation performed through comparison acute monomer levels serum 15 service members exposed repeated low-level while undergoing three-day weapons training. Amyloid precursor protein (APP) synthesis assumed be proportional additive effects within window recovery applied account cumulative predicted 6.5 ± 5.2% on average, demonstrating feasibility sensitivity blast. Outcomes discuss how modulation patient-specific factors (age, weight, genetic factors, years exposure, sleep) pathophysiological (BBB permeability, amyloidogenic pathology, neuroinflammation) can reveal potential sources variability experimental data incorporated BxK future iterations. Advancements complexity sex-specific weapon system, stress levels, risk symptom onset, pharmacological treatment strategies anticipated improve calibration. Utilization identify drivers mechanisms predict chronic outcomes has transform bTBI diagnostic, prognostic, therapeutic strategies.

Язык: Английский

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Exclusion of intracranial lesions in mild traumatic brain injury using glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1: a European multicenter study

European Journal of Emergency Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Background Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are blood biomarkers that able to aid in the assessment of mild traumatic brain injury (mTBI) patients reduce computed tomography (CT) overuse. Objectives The aim this study was evaluate predictive performance individual their combination (i.e. mTBI assay) detecting clinically significant intracranial injuries mTBI. Furthermore, influence older age on investigated. Methods This prospective multicenter conducted 12 European healthcare centers. Adults with suspected presenting emergency department (ED) each participating center within h head trauma were enrolled. GFAP UCH-L1 determined samples collected from participant. Head CT considered as reference standard for presence injury. Results assay yielded highest sensitivity [95.5%, 95% confidence interval (CI): 89.9–98.5] negative value (NPV) (97.3%, CI: 93.9–98.9) exclusion lesions sensitivities NPVs lower compared assay. In adults over 65 years, displayed weakest diagnostic performances. After optimizing cutoff values adults, following accuracy measures obtained: 87.7%, 77.2–94.5 NPV: 94.4%, 89.6–97.0 ( P < 0.001). Conclusion high NPV ED injury, performing better than biomarkers. A age-dependent performances demonstrated.

Язык: Английский

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Clinical manifestations and treatment of hypopituitarism due to traumatic brain injury

Best Practice & Research Clinical Endocrinology & Metabolism, Год журнала: 2025, Номер unknown, С. 101996 - 101996

Опубликована: Апрель 1, 2025

Язык: Английский

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Neuroimaging Characterization of Acute Traumatic Brain Injury with Focus on Frontline Clinicians: Recommendations from the 2024 National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Imaging Working Group

Journal of Neurotrauma, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Neuroimaging screening and surveillance is one of the first frontline diagnostic tools leveraged in acute assessment (first 24 h postinjury) patients suspected to have traumatic brain injury (TBI). While imaging, particular computed tomography, used almost universally emergency departments worldwide evaluate possible features TBI, there no currently agreed-upon reporting system, standard terminology, or framework contextualize imaging findings with other available medical, psychosocial, environmental data. In 2023, NIH-National Institute Neurological Disorders Stroke convened six working groups international experts TBI develop a new for nomenclature classification. The goal this effort was propose more granular system classification that incorporates recent progress biomarkers, blood-based recovery modifiers replace commonly Glasgow Coma Scale-based diagnosis mild, moderate, severe which shown relatively poor diagnostic, prognostic, therapeutic utility. Motivated by prior efforts standardize pathoanatomic research clinical trials, along studies supporting refinement originally proposed definitions, Imaging Working Group sought update expand application specifically consideration use practice. Here we report recommendations group enable translation structured common data elements care. These leverage advances technology, electronic medical record (EMR) systems, artificial intelligence (AI), input from key stakeholders, including lived experience, caretakers, providers across disciplines, radiology industry partners, policymakers. It recommended (1) would be updates definitions these should further refined as evidence underlying pathology driving signal change identified; (2) an efficient, integrated tool embedded EMR developed collaboration partners; (3) include AI-generated evidence-based feature clusters implications; (4) "patient translator" parallel assist families understanding features. addition, important disclaimers provided regarding known limitations current technology until such time they are overcome, resolution sequence parameter considerations. end multifaceted characterization model incorporating clinical, blood biomarker, psychosocial better serve not only acutely but also through postinjury continuum days, months, years follow TBI.

Язык: Английский

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The effects of hyperbaric oxygen therapy on neuroprotection and recovery after brain resuscitation

International Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. 1 - 7

Опубликована: Апрель 22, 2024

Objective: Analyze the impact of hyperbaric oxygen therapy on neuroprotection and recovery post severe traumatic brain injury (sTBI) resuscitation. Methods: Retrospective analysis clinical data from 83 sTBI patients admitted between January 2022 to 2024. Patients were divided into control (n = 41) observation 42) groups based treatment received. Control received standard therapy, while group therapy. Effects outcomes, neuroinjury markers (S100β, GFAP, UCH-L1, NSE), neurotrophic factors (NGF, BDNF), neurological function indicators (NIHSS, CSS), adverse reactions compared. Results: The showed a higher total effective rate (80.95%) compared (60.98%) (P < 0.05). Neuroinjury decreased post-treatment in both groups, with lower NGF BDNF levels increased NIHSS CSS scores No significant difference > Conclusion: Hyperbaric effectively treats by improving resuscitation success, reducing factors, enhancing promoting recovery, without increasing reaction risk.

Язык: Английский

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Management of Pediatric Mild Traumatic Brain Injury Patients: S100b, Glial Fibrillary Acidic Protein, and Heart Fatty-Acid-Binding Protein Promising Biomarkers

Neurotrauma Reports, Год журнала: 2024, Номер 5(1), С. 529 - 539

Опубликована: Май 1, 2024

Children are highly vulnerable to mild traumatic brain injury (mTBI). Blood biomarkers can help in their management. This study evaluated the performances of biomarkers, discriminating between children with mTBI who had intracranial injuries (ICIs) on computed tomography (CT+) and (1) patients without ICI (CT-) or (2) both CT- in-hospital-observation CT patients. The aim was rule out need unnecessary scans decrease length stay observation emergency department (ED). Newborns teenagers (≤16 years old) (Glasgow Coma Scale > 13) were included. S100b, glial fibrillary acidic protein (GFAP), heart fatty-acid-binding (HFABP) identify through receiver operating characteristic curves, where sensitivity set at 100%. A total 222 sampled within 6 h since trauma reported. Nineteen percent (

Язык: Английский

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Advances in development of biomarkers for brain damage and ischemia

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Июль 13, 2024

Acquired brain injury is an urgent situation that requires rapid diagnosis and treatment. Magnetic resonance imaging (MRI) computed tomography (CT) are required for accurate diagnosis. However, these methods costly require substantial infrastructure specialized staff. Circulatory biomarkers of acute may help in the management patients with cerebrovascular events prevent poor outcome mortality. The purpose this review to provide overview development potential damage increase diagnostic possibilities. For purpose, we searched PubMed database studies on biomarkers. We also accessed information from Clinicaltrials.gov identify any clinical trials biomarker measurements damage. In total, present 41 proteins, enzymes hormones have been considered as injury, which 20 studied trials. Several microRNAs emerged early Combining multiple a panel, along other parameters, yielding promising outcomes.

Язык: Английский

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High-dimensional proteomic analysis for pathophysiological classification of Traumatic Brain Injury

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 28, 2024

Abstract Pathophysiology and outcomes after Traumatic Brain Injury (TBI) are complex highly heterogenous. Current classifications uninformative about pathophysiology, which limits prognostication treatment. Fluid-based biomarkers can identify pathways proteins relevant to TBI pathophysiology. Proteomic approaches well suited exploring mechanisms of disease, as they enable sensitive assessment an expansive range proteins. We used novel high-dimensional, multiplex proteomic assays study changes in plasma protein expression acute moderate-severe TBI. analysed samples from 88 participants the longitudinal BIO-AX-TBI cohort (n=38 within 10 days injury, n=22 non-TBI trauma, n=28 non-injured controls) on two platforms: Alamar NULISA™ CNS Diseases OLINK ® Target 96 Inflammation. Participants also had data available Simoa (neurofilament light, GFAP, total tau, UCHL1) Millipore (S100B). The panel assesses 120 proteins, most have not been investigated before TBI, such differentiate trauma controls. A subset (n=29 n=24 subacute 3T MRI measures lesion volume white matter injury (fractional anisotropy, scanned 6 weeks injury). Differential Expression analysis identified 16 with TBI-specific significantly different expression. These were neuronal markers (calbindin2, UCHL1, visinin-like protein1), astroglial (S100B, GFAP), tau other neurodegenerative disease (total pTau231, PSEN1, amyloid beta42, 14-3-3γ), inflammatory cytokines (IL16, CCL2, ficolin2), cell signalling (SFRP1), metabolism (MDH1) autophagy related (sequestome1) Acute levels pTau231 correlated volume, while sequestome1 was whole skeleton fractional anisotropy CCL2 inversely corpus callosum FA. Neuronal, astroglial, each other, IL16, MDH1 sequestome1. Clustering ( k means) by 3 subgroups differential patterns, but did differ age or outcome. Proteins that overlapped platforms excellent r >0.8) correlations between values. involved processing, cellular processes autophagy. patterns thus demonstrating previously only studied animal models human Our highlights potential improve classification understanding implications for treatment development.

Язык: Английский

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Innovations in traumatic brain injury diagnostics: electrochemical impedance spectroscopy leading the way

Journal of Applied Electrochemistry, Год журнала: 2024, Номер unknown

Опубликована: Июнь 26, 2024

Язык: Английский

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Circulating Brain Injury Biomarkers for Predicting Outcomes Following Elective Neurosurgery: A Scoping Review

World Neurosurgery, Год журнала: 2024, Номер 190, С. 434 - 442.e1

Опубликована: Авг. 2, 2024

There is a need for refined methods to detect and quantify brain injuries that may be undetectable by magnetic resonance imaging neurologic examination. This review evaluates the potential efficacy of circulating injury biomarkers predicting outcomes following elective neurosurgical procedures. A comprehensive search was conducted using Cochrane, PubMed, Scopus databases. Analysis 23 relevant studies revealed specific biomarkers, including glial fibrillary acidic protein, neurofilament light chain, neuron-specific enolase, S100B, tau, are significantly associated with extent could potentially predict postsurgical outcomes. The evaluated described intracranial tumor surgeries miscellaneous interventions, demonstrated complex relationship between biomarker levels patient Circulating show promise providing objective insights into perioperative improving prognostication However, heterogeneity in study designs along lack standardized thresholds underscore further research.

Язык: Английский

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