Studies have shown that the presence of acute inflammation during recovery is indicative of poor outcomes after a traumatic brain injury (TBI); however, the role of chronic inflammation in predicting post-TBI-related symptoms remains poorly understood. The purpose of this study was to compare inflammatory biomarkers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10) in active duty personnel who either sustained or did not sustain a TBI. Service members were also assessed for post-traumatic stress disorder (PTSD), depression, and quality of life through self-reported measures. IL-6 and TNF-α concentrations were greater in the TBI group than in the control group. Of those with a TBI, IL-6 and TNF-α concentrations were greater in the high-PTSD group than the low-PTSD group. No significant differences were found in IL-10 or the IL-6/IL-10 ratios between those with low and high PTSD. Exploratory factor analysis was conducted to describe the latent structure of variables relating to emotional and physical health (i.e., Short Form 36 subcomponents, etc.) and their relationships within the TBI group with inflammatory cytokines. Four symptom profiles were found, with the third component most relating to PTSD and depression symptoms and high inflammation. This study indicates that the comorbidity of TBI and PTSD is associated with inflammation in a military sample, emphasizing the necessity for intervention in order to mitigate the risks associated with inflammation.

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.

Objective:To explore gene expression after moderate blast exposure (vs baseline) and proteomic changes after moderate- (vs low-) blast exposure.Methods:Military personnel (N = 69) donated blood for quantification of protein level, and peak pressure exposures were detected by helmet sensors before and during a blast training program (10 days total). On day 7, some participants (n = 29) sustained a moderate blast (mean peak pressure = 7.9 psi) and were matched to participants with no/low-blast exposure during the training (n = 40). PAXgene tubes were collected from one training site at baseline and day 10; RNA-sequencing day 10 expression was compared with each participant's own baseline samples to identify genes and pathways differentially expressed in moderate blast-exposed participants. Changes in amyloid precursor protein (APP) from baseline to the day of blast and following 2 days were evaluated. Symptoms were assessed using a self-reported form.Results:We identified 1,803 differentially expressed genes after moderate blast exposure; the most altered network was APP. Significantly reduced levels of peripheral APP were detected the day after the moderate blast exposure and the following day. Protein concentrations correlated with the magnitude of the moderate blast exposure on days 8 and 9. APP concentrations returned to baseline levels 3 days following the blast, likely due to increases in the genetic expression of APP. Onset of concentration problems and headaches occurred after moderate blast.Conclusions:Moderate blast exposure results in a signature biological profile that includes acute APP reductions, followed by genetic expression increases and normalization of APP levels; these changes likely influence neuronal recovery.