We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer’s disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive perf

Repeated head loading in sports is associated with negative long-term brain health, and there is growing evidence of short-term neurophysiological changes after repeated soccer heading. The objective of this study was to quantify the head kinematics and effects of repetitive soccer headers in adolescents using an instrumented mouthguard. Adolescent soccer players aged 13–18 years were randomly assigned to a kicking control, frontal heading, or oblique heading group. Participants completed neurophysiological assessments at three-time points: immediately prior to, immediately after, and approximately 24 h after completing 10 headers or kicks. The suite of assessments included the Post-Concussion Symptom Inventory, visio-vestibular exam, King-Devick test, modified Clinical Test of Sensory Interaction and Balance with force plate sway measurement, pupillary light reflex, and visual evoked potential. Data were collected for 19 participants (17 male). Frontal headers resulted in significantly higher peak resultant linear acceleration (17.4 ± 0.5 g) compared to oblique headers (12.1 ± 0.4 g, p < 0.001), and oblique headers resulted in significantly higher peak resultant angular acceleration (frontal: 1147 ± 45 rad/s², oblique: 1410 ± 65 rad/s², p < 0.001). There were no neurophysiological deficits for either heading group or significant differences from controls at either post-heading timepoint, and therefore, a bout of repeated headers did not result in changes in the neurophysiological measures evaluated in this study. The current study provided data regarding the direction of headers with the goal to reduce the risk of repetitive head loading for adolescent athletes.

There is concern that repetitive head impact exposure (RHIE) may lead to neurophysiological deficits in adolescents. Twelve high school varsity soccer players (5 female) completed the King-Devick (K-D) and complex tandem gait (CTG) assessments pre- and post-season while wearing a functional near-infrared spectroscopy (fNIRS) sensor. The average head impact load (AHIL) for each athlete-season was determined via a standardised protocol of video-verification of headband-based head impact sensor data. Linear mixed effect models were used to determine the effects of AHIL and task condition (3 K-D cards or 4 CTG conditions) on the change in mean prefrontal cortical activation measured by fNIRS, and performance on K-D and CTG, from pre- to post-season. Although there was no difference in the pre- to post-season change in K-D or CTG performance, greater AHIL was associated with greater cortical activation at post-season in comparison to pre-season during the most challenging conditions of K-D (p = 0.003) and CTG (p = 0.02), suggesting that greater RHIE necessitates increased cortical activation to complete the more challenging aspects of these assessments at the same level of performance. These results describe the effect of RHIE on neurofunction and suggest the need for further study of the time course of these effects.

Finite element (FE) modeling provides a means to examine how global kinematics of repetitive head loading in sports influences tissue level injury metrics. FE simulations of controlled soccer headers in two directions were completed using a human head FE model to estimate biomechanical loading on the brain by direction. Overall, headers were associated with 95th percentile peak maximum principal strains up to 0.07 and von Mises stresses up to 1450 Pa, and oblique headers trended toward higher values than frontal headers but below typical injury levels. These quantitative data provide insight into repetitive loading effects on the brain.

Current debate exists regarding the need for protective headwear in female lacrosse. To inform this issue, the current study quantified head impact exposure, mechanisms and kinematics in female lacrosse using instrumented mouthguards. A female high school varsity lacrosse team of 17 players wore the Stanford Instrumented Mouthguard (MiG) during 14 competitive games. Video footage was reviewed to remove false-positive recordings and verify head impacts, which resulted in a rate of 0.32 head impacts per athlete-exposure. Of the 31 video-confirmed head impacts, 54.8% were identified as stick contacts, 38.7% were player contacts and 6.5% were falls. Stick contacts had the greatest peak head kinematics. The most common impact site was the side of the head (35.5%), followed by the face/jaw (25.8%), forehead (6.5%), and crown (6.5%). Impacts to the face/jaw region of the head had significantly (p < 0.05) greater peak kinematics compared to other regions of the head, which may have resulted from the interaction of the impacting surface, or the lower jaw, and the sensor. The current study provides initial data regarding the frequency, magnitude and site of impacts sustained in female high school lacrosse. A larger sample size of high quality head impact data in female lacrosse is required to confirm these findings.

Traumatic brain injury (TBI) causes significant neurophysiological deficits and is typically associated with rapid head accelerations common in sports-related incidents and automobile accidents. There are over 1.5 million TBIs in the United States each year, with children aged 0–4 being particularly vulnerable. TBI diagnosis is currently achieved through interpretation of clinical signs and symptoms and neuroimaging; however, there is increasing interest in minimally invasive fluid biomarkers to detect TBI objectively across all ages. Pre-clinical porcine models offer controlled conditions to evaluate TBI with known biomechanical conditions and without comorbidities. The objective of the current study was to establish pediatric porcine healthy reference ranges (RRs) of common human serum TBI biomarkers and to report their acute time-course after nonimpact rotational head injury. A retrospective analysis was completed to quantify biomarker concentrations in porcine serum samples collected from 4-week-old female ( n = 215) and uncastrated male ( n = 6) Yorkshire piglets. Subjects were assigned to one of three experimental groups (sham, sagittal-single, sagittal-multiple) or to a baseline only group. A rapid nonimpact rotational head injury model was used to produce mild-to-moderate TBI in piglets following a single rotation and moderate-to-severe TBI following multiple rotations. The Quanterix Simoa Human Neurology 4-Plex A assay was used to quantify glial fibrillary acidic protein (GFAP), neurofilament light (Nf-L), tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). The 95% healthy RRs for females were calculated and validated for GFAP (6.3–69.4 pg/mL), Nf-L (9.5–67.2 pg/mL), and UCH-L1 (3.8–533.7 pg/mL). Rising early, GFAP increased significantly above the healthy RRs for sagittal-single (to 164 and 243 pg/mL) and increased significantly higher in sagittal-multiple (to 494 and 413 pg/mL) groups at 30 min and 1 h postinjury, respectively, returning to healthy RRs by 1-week postinjury. Rising later, Nf-L increased significantly above the healthy RRs by 1 day in sagittal-single (to 69 pg/mL) and sagittal-multiple groups (to 140 pg/mL) and rising further at 1 week (single = 231 pg/mL, multiple = 481 pg/mL). Sagittal-single and sagittal-multiple UCH-L1 serum samples did not differ from shams or the healthy RRs. Sex differences were observed but inconsistent. Serum GFAP and Nf-L levels had distinct time-courses following head rotations in piglets, and both corresponded to load exposure. We conclude that serum GFAP and Nf-L offer promise for early TBI diagnosis and intervention decisions for TBI and other neurological trauma.