Repetitive mild traumatic brain injury during adolescence can induce neurological dysfunction through undefined mechanisms. Interleukin-1 (IL-1) contributes to experimental adult diffuse and contusion TBI models, and IL-1 antagonists have entered clinical trials for severe TBI in adults; however, no such data exist for adolescent TBI. We developed an adolescent mouse repetitive closed head injury (rCHI) model to test the role of IL-1 family members in post-injury neurological outcome. Compared to one CHI, three daily injuries (3HD) produced acute and chronic learning deficits and emergence of hyperactivity, without detectable gliosis, neurodegeneration, brain atrophy, and white matter loss at one year. Mature IL-1β and IL-18 were induced in brain endothelium in 3HD but not 1HD, three hit weekly, or sham animals. IL-1β processing was induced cell-autonomously in three-dimensional human endothelial cell cultures subjected to in vitro concussive trauma. Mice deficient in IL-1 receptor-1 or caspase-1 had improved post-injury Morris water maze performance. Repetitive mild CHI in adolescent mice may induce behavioral deficits in the absence of significant histopathology. The endothelium is a potential source of IL-1β and IL-18 in rCHI, and IL-1 family members may be therapeutic targets to reduce or prevent neurological dysfunction after repetitive mild TBI in adolescents.

Objectives Assess changes in lower extremity musculotendinous thickness, tissue echogenicity, and muscle pennation angles among adolescent runners enrolled in a 6‐month distance running program. Methods We conducted prospective evaluations of adolescent runners' lower extremity musculotendinous changes at three timepoints (baseline, 3 months, and 6 months) throughout a progressive marathon training program. Two experienced researchers used an established protocol to obtain short‐ and long‐axis ultrasound images of the medial gastrocnemius, tibialis anterior, flexor digitorum brevis, abductor hallicus, and Achilles and patellar tendons. ImageJ software was used to calculate musculotendinous thickness and echogenicity for all structures, and fiber pennation angles for the ankle extrinsic muscles. Repeated measures within‐subject analyses of variance were conducted to assess the effect of endurance training on ultrasound‐derived measures. Results We assessed 11 runners (40.7% of eligible runners; 6F, 5M; age: 16 ± 1 years; running experience: 3 ± 2 years) who remained injury‐free and completed all ultrasound evaluation timepoints. Medial gastrocnemius muscle (F2,20 = 3.48, P = .05), tibialis anterior muscle (F2,20 = 7.36, P = .004), and Achilles tendon (F2,20 = 3.58, P = .05) thickness significantly increased over time. Echogenicity measures significantly decreased in all muscles (P‐range: <.001–.004), and increased for the patellar tendon (P < .001) during training. Muscle fiber pennation angles significantly increased for ankle extrinsic muscles (P < .001). Conclusions Adolescent runners' extrinsic foot and ankle muscles increased in volume and decreased in echogenicity, attributed to favorable distance training adaptations across the 6‐month timeframe. We noted tendon thickening without concomitantly increased echogenicity, signaling intrasubstance tendon remodeling in response to escalating distance.

Context Clinical reaction-time (RT) measures are frequently used when examining patients with concussion but do not correlate with functional movement RT. We developed the Standardized Assessment of RT (StART) to emulate the rapid cognitive demands and whole-body movement needed in sport. Objective To assess StART differences across 6 cognitive-motor combinations, examine potential demographic and health history confounders, and provide preliminary reference data for healthy collegiate student-athletes. Design Prospective, cross-sectional study. Setting Clinical medicine facilities. Patients or Other Participants A total of 89 student-athletes (56 [62.9%] men, 33 [37.1%] women; age = 19.5 ± 0.9 years, height = 178.2 ± 21.7 cm, mass = 80.4 ± 24 kg; no concussion history = 64 [71.9%]). Main Outcome Measure(s) Student-athletes completed health history questionnaires and StART during preseason testing. The StART consisted of 3 movements (standing, single-legged balance, and cutting) under 2 cognitive states (single task and dual task [subtracting by 6's or 7's]) for 3 trials under each condition. The StART trials were calculated as milliseconds between penlight illumination and initial movement. We used a 3 × 2 repeated-measures analysis of variance with post hoc t tests and 95% CIs to assess StART cognitive and movement differences, conducted univariable linear regressions to examine StART performance associations, and reported StART performance as percentiles. Results All StART conditions differed (P ≤ .03), except single-task standing versus single-task single-legged balance (P = .36). Every 1-year age increase was associated with an 18-millisecond (95% CI = 8, 27 milliseconds) slower single-task cutting RT (P &lt; .001). Female athletes had slower single-task (15 milliseconds; 95% CI = 2, 28 milliseconds; P = .02) and dual-task (28 milliseconds; 95% CI = 2, 55 milliseconds; P = .03) standing RT than male athletes. No other demographic or health history factors were associated with any StART condition (P ≥ .056). Conclusions The StART outcomes were unique across each cognitive-motor combination, suggesting minimal subtest redundancy. Only age and sex were associated with select outcomes. The StART composite scores may minimize confounding factors, but future researchers should consider age and sex when providing normative data.