Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts
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PROVIDER: S-EPMC10691880 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ImportanceSubconcussive 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.ObjectiveTo 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 participantsIn 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.ExposuresTen soccer-ball headings or kicks.Main outcomes and measuresThe 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.ResultsA 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 relevanceThese 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.Trial registrationClinicalTrials.gov Identifier: NCT03488381.
| S-EPMC7042902 | biostudies-literature
Project description:IntroductionSport-related repetitive subconcussive head impacts (RSHIs) are increasingly thought to be associated with adverse long-term outcomes. However, owing to potentially subtle effects, accurate assessment of harm to the brain as a consequence of RSHI is a major challenge and an unmet need. Several studies suggest that biofluid markers can be valuable objective tools to aid the diagnosis and injury characterisation and help in medical decision-making. Still, by and large, the results have been limited, heterogeneous and inconsistent. The main aims of this scoping review are therefore (1) to systematically examine the extent, nature and quality of available evidence from studies investigating effects of RSHI on fluid biomarkers and (2) to formulate guidelines and identify gaps with the aim to inform future clinical studies and the development of research priorities.Methods and analysesWe will use a comprehensive search strategy to retrieve all available and relevant articles in the literature. The following electronic databases will be systematically searched: MEDLINE (EBSCO host; from 1809 to 2020); Scopus (from 1788 to 2020); SPORTDiscus (from 1892 to 2020); CINAHL Complete (from 1937 to 2020); PsycINFO (from 1887 to 2020); Cochrane Library (to 2020); OpenGrey (to 2020); ClinicalTrials.gov (to 2020) and WHO International Clinical Trials Registry Platform (to 2020). We will consider primarily biomedical studies evaluating the biofluid markers following RSHI. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. Disagreements will be resolved through consensus or arbitrated by a third reviewer if necessary. Data will be reported qualitatively given the heterogeneity of the included studies. In synthesising the evidence, we will structure results by markers, sample types, outcomes, sport and timepoints.Ethics and disseminationEthics approval is not required. We will submit results for peer-review publication, and present at relevant conferences.
| S-EPMC8240577 | biostudies-literature
Project description:This was an exploratory study designed to evaluate the feasibility of a recently established imaging modality, quantitative ultrashort time-to-echo contrast enhanced (QUTE-CE), to follow the early pathology and vulnerability of the blood brain barrier in response to single and repetitive mild head impacts. A closed-head, momentum exchange model was used to produce three consecutive mild head impacts aimed at the forebrain separated by 24 h each. Animals were measured at baseline and within 1 h of impact. Anatomical images were collected to assess the extent of structural damage. QUTE-CE biomarkers for BBB permeability were calculated on 420,000 voxels in the brain and were registered to a bilateral 3D brain atlas providing site-specific information on 118 anatomical regions. Blood brain barrier permeability was confirmed by extravasation of labeled dextran. All head impacts occurred in the absence of any structural brain damage. A single mild head impact had measurable effects on blood brain barrier permeability and was more significant after the second and third impacts. Affected regions included the prefrontal ctx, basal ganglia, hippocampus, amygdala, and brainstem. Our findings support the concerns raised by the healthcare community regarding mild head injuries in participants in organized contact sports and military personnel in basic training and combat.
| S-EPMC8515019 | biostudies-literature
Project description:The brain vital signs framework is a portable, objective, neurophysiological evaluation of brain function at point-of-care. We investigated brain vital signs at pre- and post-season for age 14 or under (Bantam) and age 16-20 (Junior-A) male ice hockey players to (i) further investigate previously published brain vital sign results showing subconcussive cognitive deficits and (ii) validate these findings through comparison with head-impact data obtained from instrumented accelerometers. With a longitudinal study design, 23 male ice hockey players in Bantam (n = 13; age 13.63 ± 0.62) and Tier II Junior-A (n = 10; age 18.62 ± 0.86) divisions were assessed at pre- and post-season. None were diagnosed with a concussion during the season. Cognitive evoked potential measures of Auditory sensation (N100), Basic attention (P300) and Cognitive processing (N400) were analysed as changes in peak amplitudes and latencies (six standard scores total). A regression analysis examined the relationship between brain vital signs and the number of head impacts received during the study season. Significant pre/post differences in brain vital signs were detected for both groups. Bantam and Junior-A players also differed in number of head impacts (Bantam: 32.92 ± 17.68; Junior-A: 195.00 ± 61.08; P < 0.001). Importantly, the regression model demonstrated a significant linear relationship between changes in brain vital signs and total head impacts received (R = 0.799, P = 0.007), with clear differences between the Bantam and Junior-A groups. In the absence of a clinically diagnosed concussion, the brain vital sign changes appear to have demonstrated the compounding effects of repetitive subconcussive impacts. The findings underscored the importance of an objective physiological measure of brain function along the spectrum of concussive impacts.
| S-EPMC8023684 | biostudies-literature
Project description:IntroductionThis clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute subconcussive head impacts.MethodsThe present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (n = 30). Soccer players without ADHD were assigned into a non-ADHD group (n = 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading.ResultsThere were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC: p = 0.019; KDT: p = 0.018), and persisted at 2 h-post (NPC: p = 0.007; KDT: p = 0.014) and 24 h-post heading (NPC: p = 0.001). NPC significantly worsened over time in both groups compared to baseline [ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69), p < 0.001; 24 h-post, 1.68 cm, 95%CI:(1.22, 2.13), p = 0.001; Non-ADHD: 2 h-post, 0.96 cm, 95%CI:(0.50, 1.42), p < 0.001; 24 h-post, 1.09 cm, 95%CI:(0.63, 1.55), p < 0.001]. Conversely, improvements in KDT time compared to baseline occurred at 2 h-post in the non-ADHD group [-1.32 s, 95%CI:(-2.55, -0.09), p = 0.04] and at 24 h-post in both groups [ADHD: -4.66 s, 95%CI:(-5.89, -3.43), p < 0.001; Non-ADHD: -3.46 s, 95%CI:(-4.69, -2.23), p < 0.001)]. There were no group-by-time interactions for GFAP as both groups exhibited increased levels at 2 h-post [ADHD: 7.75 pg./mL, 95%CI:(1.41, 14.10), p = 0.019; Non-ADHD: 7.91 pg./mL, 95%CI:(1.71, 14.14), p = 0.015)] that returned to baseline at 24 h-post. NF-L levels increased at 2 h-post heading in the ADHD group [0.45 pg./mL, 95%CI:(0.05, 0.86), p = 0.032], but no significant NF-L changes were observed in the non-ADHD group over time.DiscussionTen soccer headers elevated GFAP levels and NPC impairment in both groups. However, persisting group difference in NPC, blunted KDT performance, and increased NF-L levels in the ADHD group suggest that ADHD may reduce neuro-ophthalmologic function and heighten axonal response to soccer headers.Clinical trial registrationClinicalTrials.gov, identifier ID: (NCT04880304).
| S-EPMC10710155 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a major health concern in the United States and globally, contributing to disability and long-term neurological problems. Lipid dysregulation after TBI is underexplored, and a better understanding of lipid turnover and degradation could point to novel biomarker candidates and therapeutic targets. Here, we investigated overlapping lipidome changes in the brain and blood using a data-driven discovery approach to understand lipid alterations in the brain and serum compartments acutely following mild TBI (mTBI) and the potential efflux of brain lipids to peripheral blood. The cortices and sera from male and female Sprague-Dawley rats were analyzed via ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) in both positive and negative ion modes following single and repetitive closed head impacts. The overlapping lipids in the data sets were identified with an in-house data dictionary for investigating lipid class changes. MS-based lipid profiling revealed overall increased changes in the serum compartment, while the brain lipids primarily showed decreased changes. Interestingly, there were prominent alterations in the sphingolipid class in the brain and blood compartments after single and repetitive injury, which may suggest efflux of brain sphingolipids into the blood after TBI. Genetic algorithms were used for predictive panel selection to classify injured and control samples with high sensitivity and specificity. These overlapping lipid panels primarily mapped to the glycerophospholipid metabolism pathway with Benjamini-Hochberg adjusted q-values less than 0.05. Collectively, these results detail overlapping lipidome changes following mTBI in the brain and blood compartments, increasing our understanding of TBI-related lipid dysregulation while identifying novel biomarker candidates.
| S-EPMC10797623 | biostudies-literature
Project description:Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data. Four datasets were centrally pooled to perform uniform quality control and data preprocessing. A total of 131 non-concussed active athletes (American football, rugby, ice hockey; mean age: 20.06 ± 2.06 years) with baseline and post-season data were included. Nonparametric permutation inference (one-sample t tests, one-sided) was applied to analyze the difference maps of multiple diffusion parameters. The analyses revealed widespread lateralized patterns of sports-season-related increases and decreases in mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across spatially distinct white matter regions. Increases were shown across one MD-cluster (3195 voxels; mean change: 2.34%), one AD-cluster (5740 voxels; mean change: 1.75%), and three RD-clusters (817 total voxels; mean change: 3.11 to 4.70%). Decreases were shown across two MD-clusters (1637 total voxels; mean change: -1.43 to -1.48%), two RD-clusters (1240 total voxels; mean change: -1.92 to -1.93%), and one AD-cluster (724 voxels; mean change: -1.28%). The resulting pattern implies the presence of strain-induced injuries in central and brainstem regions, with comparatively milder physical exercise-induced effects across frontal and superior regions of the left hemisphere, which need further investigation. This article highlights key considerations that need to be addressed in future work to enhance our understanding of the nature of observed white matter changes, improve the comparability of findings across studies, and promote data pooling initiatives to allow more detailed investigations (e.g., exploring sex- and sport-specific effects).
| S-EPMC11345636 | biostudies-literature
Project description:The changes in brain function in response to mild head injury are usually subtle and go undetected. Physiological biomarkers would aid in the early diagnosis of mild head injury. In this study we used hypercapnia to follow changes in cerebral vascular reactivity after repetitive mild head injury. We hypothesized head injury would reduce vascular reactivity. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days. All head impacts were delivered while rats were fully awake under red light illumination. There was no neuroradiological evidence of brain damage. After the 3rd impact rats were exposed to 5% CO2 and imaged for changes in BOLD signal. All imaging was done while rats were awake without the confound of anesthesia. The data were registered to a 3D MRI rat atlas with 171 segmented brain areas providing site specific information on vascular reactivity. The changes in vascular reactivity were not uniform across the brain. The prefrontal cortex, somatosensory cortex and basal ganglia showed the hypothesized decrease in vascular reactivity while the cerebellum, thalamus, brainstem, and olfactory system showed an increase in BOLD signal to hypercapnia.
| S-EPMC11422282 | biostudies-literature
Project description:BackgroundNeuroinflammation is a prominent pathological hallmark of traumatic brain injury (TBI) and glia cells have been widely characterized in the onset or progression of brain inflammation. While an effect of inflammation on cerebrovascular breakdown has been observed, little is known about the specific contribution of brain pericytes to the inflammatory response in TBI. Here, we focused on studying the pericyte response to inflammatory stimuli commonly found in the brain following TBI.MethodsMouse brain vascular pericytes were exposed to IL-1β, TNF-α and IFN-γ for 2 h and 24 h and probed for markers of pericyte health and a panel of inflammatory mediators. As the platelet-derived growth factor (PDGF) pathway is critical to pericyte function, we also assessed the effect of PDGF-BB stimulation on the inflammatory response in pericytes. Cultured pericytes were treated with PDGF-BB (10 ng/mL) prior to, simultaneously, and following inflammatory insult. To further investigate their role in brain immunosurveillance, we analyzed the cytokine secretome in mouse pericyte cultures treated with PDGF-BB, as well as in brain vascular pericytes isolated from repetitive mild TBI (r-mTBI) mice that were fed phenytoin-enriched chow, an inducer of PDGF-BB secretion.ResultsCytokine stimulation with TNF-α, IL-1β, and IFN-γ for 2 and 24 h led to significant upregulation of PDGFRβ in cultured pericytes, with an 8-fold increase after 24 h. MTT assays showed no significant change in cell viability, indicating that cytokine treatment did not induce cytotoxicity. Further, elevated levels of pro-inflammatory markers STAT1 and p-NFkB were observed in response to cytokine exposure, with a concurrent increase in VCAM1 and MMP9 expression. PDGF-BB treatment significantly attenuated the inflammatory response in pericytes, reducing PDGFRβ levels and the activation of inflammatory pathways, including STAT1 and NFkB. Cytokine secretion profiles also revealed that PDGF-BB, when administered post-inflammatory insult, selectively reduced pro-inflammatory cytokines such as IL-1β and IFN-γ. Additionally, phenytoin treatment in r-mTBI mice decreased IL-1β, TNF-α, IL-5, and KC/GRO levels in isolated brain pericytes, while IL-2, IL-4, and IL-6 levels were unchanged compared to untreated r-mTBI animals.ConclusionsOur results indicate an immunoreactive role for brain pericytes in the propagation of neuroinflammation. Moreover, following brain insults, we found PDGF-BB stimulation can normalize pericyte function and reduce cerebrovascular inflammation, a key factor in secondary brain injury. Targeting brain pericytes may provide novel therapeutic opportunities to improve cerebrovascular health and reduce brain inflammation in the aftermath of TBI.
| S-EPMC11877937 | biostudies-literature
Project description: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.
| S-EPMC6459945 | biostudies-literature