Inflammation Relates to Chronic Behavioral and Neurological Symptoms in Military with Traumatic Brain Injuries.

Devoto, Christina; Arcurio, Lindsay; Fetta, Joseph; Ley, Mary; Rodney, Tamar; Kanefsky, Rebekah; Gill, Jessica

doi:10.3727/096368916x693455

Cited by 13 publications

(16 citation statements)

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“…This is concerning, because in animal model blast-induced TBI (biTBI) has different signature features than blunt-force TBI (Courtney and Courtney, 2015). Previously, we have linked chronic neurological symptoms related to a combination of blast and TBIs in military personnel to greater inflammation, suggesting that inflammation may contribute to blast related pathology, yet no acute clinical studies to understand this relationship have been undertaken (Devoto et al, 2016). Therefore, clinical studies such as the one presented here are necessary to better understand how inflammatory changes shape both recovery, as well as pathology, following blast exposure without the impact of physical injuries, including blunt force TBIs.…”

Section: Introductionmentioning

confidence: 99%

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

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A unique cohort of military personnel exposed to isolated blast was studied to explore acute peripheral cytokine levels, with the aim of identifying blast-specific biomarkers. Several cytokines, including interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNFα) have been linked to pre-clinical blast exposure, but remained unstudied in clinical blast exposure. To address this gap, blood samples from 62 military personnel were obtained at baseline, and daily, during a 10-day blast-related training program; changes in the peripheral concentrations of IL-6, IL-10 and TNFα were evaluated using an ultrasensitive assay. Two groups of trainees were matched on age, duration of military service, and previous history of blast exposure(s), resulting in moderate blast cases and no/low blast controls. Blast exposures were measured using helmet sensors that determined the average peak pressure in pounds per square inch (psi). Moderate blast cases had significantly elevated concentrations of IL-6 (F1,60 =18.81, p < 0.01) and TNFα (F1,60 =12.03, p < 0.01) compared to no/low blast controls; levels rebounded to baseline levels the day after blast. On the day of the moderate blast exposure, the extent of the overpressure (psi) in those exposed correlated with IL-6 (r = 0.46, p < 0.05) concentrations. These findings indicate that moderate primary blast exposure results in changes, specifically acute and transient increases in peripheral inflammatory markers which may have implications for neuronal health.

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Section: Introductionmentioning

confidence: 99%

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Gill

Motamedi

Osier

et al. 2017

Brain, Behavior, and Immunity

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“…Interestingly, the study also showed that levels of IL-8 increased among cases from 6 months to 12 months. Devoto and colleagues reported elevated serum levels of IL-6, IL-10, and TNF-α among bTBI cases compared with controls during the recovery period, post-injury [45]. Serum samples were obtained within 16 months after deployment, but the timing of the specimen collection during recovery phase in relation to the bTBI diagnosis was not described.…”

Section: Discussionmentioning

confidence: 99%

“…There is a paucity of human data on the systemic cytokine immune response during the acute phase [26,44] or during later time points specific for bTBI [45]. Better characterization of the cytokine response in peripheral serum during recovery post-bTBI would help clarify the systemic inflammatory processes during the chronic phase, may provide better monitoring of the recovery or rehabilitative period, and may possibly identify and evaluate therapeutic interventions [46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members

Rusiecki

Levin

Wang

et al. 2020

J Neuroinflammation

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Background: There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury. Methods: We conducted a repeated measures, case-control study, examining associations of serum levels of proand anti-inflammatory cytokines, measured both pre-and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISAbased array for 15 cytokines. We compared pre-vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired ttests and generalized linear models. Results: The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From preto post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (μ = − 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (μ = − 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (μ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (μ = − 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (μ = 1859.60 pg/ml; s.e. = 1737.51) from pre-to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre-to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases. Conclusion: The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.

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“…Beyond pairwise comparison, iterative EFA simplified profiles of 10 markers, clustering them by underlying relationships as previously done with TBI patient comorbidities. 46 This unsupervised analysis grouped nine neurotrauma markers into two factors, with CSF standard PTGDS resulting in a third factor. Altogether, the three factors accounted for 84% of the cohort's data variance.…”

Section: Aid Biomarker Concentrations Are Measured Using Protein and mentioning

confidence: 99%

New astroglial injury-defined biomarkers for neurotrauma assessment

Halford

Shen

Itamura

et al. 2017

J Cereb Blood Flow Metab

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Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.

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Inflammation Relates to Chronic Behavioral and Neurological Symptoms in Military with Traumatic Brain Injuries.

Cited by 13 publications

References 0 publications

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members

New astroglial injury-defined biomarkers for neurotrauma assessment

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