Brain-related proteins as serum biomarkers of acute, subconcussive blast overpressure exposure: A cohort study of military personnel

Abstract

Repeated exposure to blast overpressure remains a major cause of adverse health for military personnel who, as a consequence, are at a higher risk for neurodegenerative disease and suicide. Acute, early tracking of blast related effects holds the promise of rapid health assessment prior to onset of chronic problems. Current techniques used to determine blastrelated effects rely upon reporting of symptomology similar to that of concussion and neurocognitive assessment relevant to operational decrement. Here, we describe the results of a cross sectional study with pared observations. The concentration of multiple TBI-related proteins was tested in serum collected within one hour of blast exposure as a quantitative and minimally invasive strategy to augment assessment of blast-exposure effects that are associated with concussion-like symptomology and reaction time decrements. We determined that median simple reaction time (SRT) was slowed in accordance with serum Nf-L, tau, Aβ-40, and Aβ-42 elevation after overpressure exposure. In contrast, median levels of serum GFAP decreased. Individual, inter-subject analysis revealed positive correlations between changes in Nf-L and GFAP, and in Aβ-40 compared to Aβ-42. The change in Nf-L was negatively associated with tau, Aβ-40, and Aβ-42. Participants reported experiencing headaches, dizziness and taking longer to think. Dizziness was associated with reaction time decrements, GFAP or NfL suppression, as well as Aβ peptide elevation. UCH-L1 elevation had a weak association with mTBI/concussion history. Multiplexed serum biomarker quantitation, coupled with reaction time assessment and symptomology determined before and after blast exposure, may serve as a platform for tracking adverse effects in the absence of a head wound or diagnosed concussion. We propose further evaluation of serum biomarkers, which are often associated with TBI, in the context of acute operational blast exposures.

Overpressure Exposure From .50-Caliber Rifle Training Is Associated With Increased Amyloid Beta Peptides in Serum

“…This time-dependent observation is often overlooked and may indicate that acute (e.g., hourly) temporal dynamics of Nf-L may be useful in monitoring early phase OP-mediated effects when compared to a participant's basal biomarker levels, whereas leakage of a fairly large protein from the CNS is useful in the context of a known variable (e.g., clinical TBI diagnosis) during longer timeframes (e.g., weeks-months). Our group has previously reported that serum GFAP levels also decreased in accordance with persistent concussion-like symptomology after mild-to-moderate OP exposure caused by blast (34). Replication of both observations with larger cohorts and variation of peak OP levels and assessment of medical relevance compared to basal levels is ongoing.…”

Penetrating Ballistic-Like Brain Injury Leads to MicroRNA Dysregulation, BACE1 Upregulation, and Amyloid Precursor Protein Loss in Lesioned Rat Brain Tissues

“…Severe traumatic brain injury (TBI) remains a significant health issue that leads to cognitive and physical impairment, prolonged hospitalization, and the need for long-term care (Langlois et al, 2005;Zaloshnja et al, 2008;Cuthbert et al, 2015;Taylor et al, 2017). Military personnel are at a particularly high risk for encountering a TBI (Santiago et al, 2012) due, in part, to improvised explosive devices and munition exposures (Meyer et al, 2010;Boutte et al, 2019). Patients who suffer from a TBI are at a much higher risk of developing neurodegenerative disease or dementia (Plassman et al, 2000), particularly Alzheimer's disease (AD) (Mendez et al, 2015), Parkinson's disease (PD) (Gardner et al, 2018), Amyotrophic lateral sclerosis (ALS) (Franz et al, 2019), psychological disorders (Veitch et al, 2013), post-traumatic stress disorder (PTSD) (Friedemann-Sanchez et al, 2008), and suicide (Goldstein and Diaz-Arrastia, 2018).…”

Factors Contributing to Increased Blast Overpressure inside Modern Ballistic Helmets

“…The blast wave propagation inside combat helmets is a complex problem, with the pressure focusing under the helmet dependent on several factors: 1) the shape of the helmet; 2) orientation relative to the source of the blast wave, and 3) the suspension system (i.e., number of pads, their distribution under the helmet and material properties). The mounting evidence suggests an association between occupational low-level blast exposure and acute adverse neurological effects [26], and related serum biomarkers changes [27,28]. The role of the helmet in the development of these effects is unclear at this time.…”