Association of Increased Serum S100B Levels With High School Football Subconcussive Head Impacts

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k-means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 μg/L; interquartile-range, 0.011–0.043 μg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 μg/L vs. 0.019 ± 0.017 μg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports

Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study

While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts

The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.National Institutes of Health (U.S.) (grant AI078092)National Institutes of Health (U.S.) (grant AI068655

Preliminary evidence-based recommendations for return to learn: a novel pilot study tracking concussed college students

Aim: Students re-entering the academic setting after a concussion is commonly referred to as return-to-learn and, to date, very few studies have examined the return-to-learn aspect of concussion recovery. Methodology: Nine college-aged, full-time students who were diagnosed with concussions were monitored throughout their concussion recovery. The severity for five chief symptoms (headache, dizziness, difficulty concentrating, fatigue, anxiety) were recorded six-times per day through text messages, and daily phone calls recorded participant's behavioral traits. Results: We identified five behavioral variables which significantly influenced symptom resolution (music, sleep, physical activity, water and time) (p = 0.0004 to p = 0.036). Additionally, subjects reported math and computer-oriented courses as the most difficult (33 and 44%, respectively). Conclusion: We introduce a novel approach to monitor concussed students throughout their recovery, as well as factors that may influence concussion recovery process

Does acute soccer heading cause an increase in plasma S100B? A randomized controlled trial.

The purpose of this study was to test the effect of subconcussive head impacts on acute changes in plasma S100B. In this randomized controlled trial, 79 healthy adult soccer players were randomly assigned to either the heading (n = 41) or kicking-control groups (n = 38). The heading group executed 10 headers with soccer balls projected at a speed of 25 mph, whereas the kicking-control group performed 10 kicks. Plasma samples were obtained at pre-, 0h post-, 2h post- and 24h post-intervention and measured for S100B. The primary hypothesis was that there would be a significant group difference (group-by-time interaction) in plasma S100B at 2h post-intervention. Secondary hypotheses included (1) no significant group differences in plasma S100B concentrations at 0h post- and 24h post-intervention; (2) a significant within-group increase in S100B concentrations in the heading group at 2h post-intervention compared to pre-intervention; and (3) no significant within-group changes in plasma S100B in the kicking-control group. Data from 68 subjects were available for analysis (heading n = 37, kicking n = 31). There were no differences in S100B concentrations between heading and kicking groups over time, as evidenced by nonsignificant group-by-time interaction at 2h post-intervention (B = 2.20, 95%CI [-22.22, 26.63], p = 0.86) and at all the other time points (0h post: B = -11.05, 95%CI [-35.37, 13.28], p = 0.38; 24h post: B = 16.11, 95%CI [-8.29, 40.51], p = 0.20). Part of the secondary outcome, the heading group showed elevation in plasma S100B concentrations at 24h post-intervention compared to pre-heading baseline (B = 19.57, 95%CI [3.13, 36.02], p = 0.02), whereas all other within-group comparisons in both remained nonsignificant. The data suggest that 10 bouts of acute controlled soccer headings do not elevate S100B concentrations up to 24-hour post-heading. Further dose-response studies with longer follow-up time points may help determine thresholds of acute soccer heading exposure that are related to astrocyte activation. The protocol was registered under ClinicalTrials.gov (NCT03488381; retrospectively registered.)

Neuro-Ophthalmologic Response to Repetitive Subconcussive Head Impacts

Importance: Subconcussive head impacts have emerged as a complex public health concern. The oculomotor system is sensitive to brain trauma; however, neuro-ophthalmologic response to subconcussive head impacts remains unclear. Objective: To examine whether subconcussive head impacts cause impairments in neuro-ophthalmologic function as measured by the King-Devick test (KDT) and oculomotor function as measured by the near point of convergence. Design, setting, and participants: In this randomized clinical trial, adult soccer players were randomized into either a heading group or kicking (control) group. The heading group executed 10 headers with soccer balls projected at a speed of 25 mph. The kicking-control group followed the same protocol but with 10 kicks. Peak linear and rotational head accelerations were assessed with a triaxial accelerometer. The KDT speed and error and near point of convergence were assessed at baseline (preheading or prekicking) and at 0, 2, and 24 hours after heading or kicking. Exposures: Ten soccer-ball headings or kicks. Main outcomes and measures: The primary outcome was the group-by-time interaction of KDT speed at 0 hours after heading or kicking. The secondary outcomes included KDT speed at 2 hours and 24 hours after heading or kicking, KDT error, and near point of convergence. Results: A total of 78 individuals enrolled (heading group, n = 40; kicking-control group, n = 38). Eleven individuals (heading group: 4 women; mean [SD] age, 22.5 [1.0] years; kicking-control group, 3 women and 4 men; mean [SD] age, 20.9 [1.1] years) voluntarily withdrew from the study. Data from 67 participants with a mean (SD) age of 20.6 (1.7) years were eligible for analysis (heading, n = 36; kicking-control, n = 31). Mean (SD) peak linear accelerations and peak rotational accelerations per impact for the heading group were 33.2 (6.8) g and 3.6 (1.4) krad/s2, respectively. Conversely, soccer kicking did not induce a detectable level of head acceleration. Both groups showed improvements in KDT speed (heading group: 0 hours, -1.2 [95% CI, -2.2 to -0.1] seconds; P = .03; 2 hours, -1.3 [95% CI, -2.6 to 0] seconds; P = .05; 24 hours, -3.2 [95% CI, -4.3 to -2.2] seconds; P < .001; kicking-control group: 0 hours, -3.3 [95% CI, -4.1 to -2.5] seconds; P < .001; 2 hours, -4.1 [95% CI, -5.1 to -3.1] seconds; P < .001; 24 hours, -5.2 [95% CI, -6.2 to -4.2] seconds; P < .001). Group differences occurred at all postintervention points; the kicking-control group performed KDT faster at 0 hours (-2.2 [95% CI, -0.8 to -3.5] seconds; P = .001), 2 hours (-2.8 [95% CI, -1.2 to -4.4] seconds; P < .001), and 24 hours after the intervention (-2.0 [95% CI, -0.5 to -3.4] seconds; P = .007) compared with those of the heading group. Conclusions and relevance: These data support the hypothesis that neuro-ophthalmologic function is affected, at least in the short term, by subconcussive head impacts that may affect some individuals in some contact sports. Further studies may help determine if these measures can be a useful clinical tool in detecting acute subconcussive injury