Repetitive Injury Research Articles

Profiling the neuroimmune cascade in 3xTg-AD mice exposed to successive mild traumatic brain injuries

Repetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta (Aβ) plaques, gliosis, and neuronal and functional loss. However, a comprehensive study relating acute changes in immune signaling and glial reactivity to neuronal changes and pathological markers after single and repetitive mTBIs is currently lacking. In the current study, we addressed the question of how repeated injuries affect the brain neuroimmune response in the acute phase of injury (< 24 h) by exposing the 3xTg-AD mouse model of tau and Aβ pathology to successive (1x-5x) once-daily weight drop closed-head injuries and quantifying immune markers, pathological markers, and transcriptional profiles at 30 min, 4 h, and 24 h after each injury. We used young adult 2–4 month old 3xTg-AD mice to model the effects of rmTBI in the absence of significant tau and Aβ pathology. We identified pronounced sexual dimorphism in this model, with females eliciting more diverse changes after injury compared to males. Specifically, females showed: (1) a single injury caused a decrease in neuron-enriched genes inversely correlated with inflammatory protein expression and an increase in AD-related genes within 24 h, (2) each injury significantly increased a group of cortical cytokines (IL-1α, IL-1β, IL-2, IL-9, IL-13, IL-17, KC) and MAPK phospho-proteins (phospho-Atf2, phospho-Mek1), several of which co-labeled with neurons and correlated with phospho-tau, and (3) repetitive injury caused increased expression of genes associated with astrocyte reactivity and macrophage-associated immune function. Collectively our data suggest that neurons respond to a single injury within 24 h, while other cell types, including astrocytes, transition to inflammatory phenotypes within days of repetitive injury.

Glucose attenuates the long-term adverse neurodevelopment effect of neonate pain stimulus via CRF/GR in rats

BackgroundNeonates undergo numerous painful procedures throughout their hospitalization. Repeated procedural pain may cause adverse long-term effects. Glucose as a non-pharmacological analgesia, is used for neonate pain management. In this study, potential mechanism of attenuate pain induced by glucose in neurodevelopment effect of neonate pain stimulus was investigated. MethodsNeonatal rats to perform a repetitive injury model and glucose intervention model in the postnatal day 0–7(P0-7). Pain thresholds were measured by von Frey test weekly. The puberty behavioral outcome, tissue loss and protein expression in hippocampus were analyzed. ResultsOral administration of glucose after repeated pain stimulation can maintain the hippocampal structure in, and reduce the expressions of corticotropin releasing factor (CFR) and glucocorticoid receptor (GR), therefore, resulted in long-term threshold of pain and cognitive improvement. ConclusionExposure to neonatal repeated procedural pain causes persistent mechanical hypersensitivity and the dysfunction of spatial memory retention at puberty. In addition, glucose can relieve these adverse effects, possibly via decreasing CRF/GR levels to change the hypothalamus-pituitary-adrenal (HPA) axis.

Concussion burden and later-life cardiovascular risk factors in former professional American-style football players.

Mid-life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American-style football (ASF) players. In a cross-sectional study of 4080 professional ASF players conducted between January 2015 and March 2022, we used an mulitsymptom concussion symptom score (CSS) and the number of loss-of-consciousness (LOC) episodes as a single severe symptom to quantify football-related concussion exposure. Primary outcomes were hypertension, dyslipidemia, and diabetes, defined by current or recommended prescription medication use. The prevalence of hypertension, high cholesterol, and diabetes among former players (52 ± 14 years of age) was 37%, 34%, and 9%. Concussion burden was significantly associated with hypertension (lowest vs. highest CSS quartile, odds ratio (OR) = 1.99; 95%CI: 1.33-2.98; p < 0.01) and high cholesterol (lowest vs. moderate CSS, OR = 1.46, 95%CI, 1.11-1.91; p < 0.01), but not diabetes. In fully adjusted models, the prevalence of multiple CVD was associated with CSS. These results were driven by younger former players (≤ 40 year of age) in which the odds of hypertension were over three times higher in those in the highest CSS quartile (OR = 3.29, 95%CI: 1.39-7.61; p = 0.01). Results were similar for LOC analyses. Prior concussion burden is associated with postcareer atherogenic cardiovascular risk profiles among former professional American football players.

Health problems among elite Dutch youth long track speed skaters: a one-season prospective study

ObjectivesTo describe the frequency, type, and severity of health problems in long-track speed skating to inform injury prevention strategies.MethodsWe prospectively collected weekly health and sport exposure data on 84 highly...

Prevalence of Work-Related Repetitive Stress Injuries amongst the Health Care Workers in Large Tertiary Care Hospital

Prevalence of Work-Related Repetitive Stress Injuries amongst the Health Care Workers in Large Tertiary Care Hospital

Pegylated polymeric micelles of boswellic acid-selenium mitigates repetitive mild traumatic brain injury: Regulation of miR-155 and miR-146a/BDNF/ Klotho/Foxo3a cue

This study aims to explore the protective machinery of pegylated polymeric micelles of boswellic acid-selenium (PMBS) against secondary neuronal damage triggered by mild repetitive traumatic brain injury (RTBI). After PMBS characterization in terms of particle size, size distribution, zeta potential, and transmission electronic microscopy, the selected formula was used to investigate its potency against experimental RTBI. Five groups of rats were used; group 1 (control) and the other four groups were subjected to RTBI. Groups 2 was RTBI positive control, while 3, 4, and 5 received boswellic acid (BSA), selenium (SEL), and PMBS, respectively. The open-field behavioral test was used for behavioral assessment. Subsequently, brain tissues were utilized for hematoxylin and eosin staining, Nissl staining, Western blotting, and ELISA in addition to evaluating microRNA expression (miR-155 and miR-146a). The behavioral changes, oxidative stress, and neuroinflammation triggered by RTBI were all improved by PMBS. Moreover, PMBS mitigated excessive glutamate-induced excitotoxicity and the dysregulation in miR-155 and miR-146a expression. Besides, connexin43 (Cx43) expression as well as klotho and brain-derived neurotrophic factor (BDNF) were upregulated with diminished neuronal cell death and apoptosis because of reduced Forkhead Box class O3a(Foxo3a) expression in the PMBS-treated group. The current study has provided evidence of the benefits produced by incorporating BSA and SEL in PEGylated polymeric micelles formula. PMBS is a promising therapy for RTBI. Its beneficial effects are attributed to the manipulation of many pathways, including the regulation of miR-155 and miR-146a expression, as well as the BDNF /Klotho/Foxo3a signaling pathway.

High-salt diet induces microbiome dysregulation, neuroinflammation and anxiety in the chronic period after mild repetitive closed head injury in adolescent mice.

The associations between human concussions and subsequent sequelae of chronic neuropsychiatric and cardiovascular diseases such as hypertension have been reported; however, little is known about the underlying biological processes. We hypothesized that dietary changes, including a high-salt diet, disrupt the bidirectional gut-brain axis, resulting in worsening neuroinflammation and emergence of cardiovascular and behavioural phenotypes in the chronic period after repetitive closed head injury in adolescent mice. Adolescent mice were subjected to three daily closed head injuries, recovered for 12 weeks and then maintained on a high-salt diet or a normal diet for an additional 12 weeks. Experimental endpoints were haemodynamics, behaviour, microglial gene expression (bulk RNA sequencing), brain inflammation (brain tissue quantitative PCR) and microbiome diversity (16S RNA sequencing). High-salt diet did not affect systemic blood pressure or heart rate in sham or injured mice. High-salt diet increased anxiety-like behaviour in injured mice compared to sham mice fed with high-salt diet and injured mice fed with normal diet. Increased anxiety in injured mice that received a high-salt diet was associated with microgliosis and a proinflammatory microglial transcriptomic signature, including upregulation in interferon-gamma, interferon-beta and oxidative stress-related pathways. Accordingly, we found upregulation of tumour necrosis factor-alpha and interferon-gamma mRNA in the brain tissue of high salt diet-fed injured mice. High-salt diet had a larger effect on the gut microbiome composition than repetitive closed head injury. Increases in gut microbes in the families Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae were positively correlated with anxiety-like behaviours. In contrast, Muribaculaceae, Acholeplasmataceae and Lactobacillaceae were negatively correlated with anxiety in injured mice that received a high-salt diet, a time-dependent effect. The findings suggest that high-salt diet, administered after a recovery period, may affect neurologic outcomes following mild repetitive head injury, including the development of anxiety. This effect was linked to microbiome dysregulation and an exacerbation of microglial inflammation, which may be physiological targets to prevent behavioural sequelae in the chronic period after mild repetitive head injury. The data suggest an important contribution of diet in determining long-term outcomes after mild repetitive head injury.

Advanced Swine Management: Infrared Imaging for Precise Localization of Reproductive Organs in Livestock Monitoring

Traditional methods for predicting sow reproductive cycles are not only costly but also demand a larger workforce, exposing workers to respiratory toxins, repetitive stress injuries, and chronic pain. This occupational hazard can even lead to mental health issues due to repeated exposure to violence. Managing health and welfare issues becomes pivotal in group-housed animal settings, where individual care is challenging on large farms with limited staff. The necessity for computer vision systems to analyze sow behavior and detect deviations indicative of health problems is apparent. Beyond observing changes in behavior and physical traits, computer vision can accurately detect estrus based on vulva characteristics and analyze thermal imagery for temperature changes, which are crucial indicators of estrus. By automating estrus detection, farms can significantly enhance breeding efficiency, ensuring optimal timing for insemination. These systems work continuously, promptly alerting staff to anomalies for early intervention. In this research, we propose part of the solution by utilizing an image segmentation model to localize the vulva. We created our technique to identify vulvae on pig farms using infrared imagery. To accomplish this, we initially isolate the vulva region by enclosing it within a red rectangle and then generate vulva masks by applying a threshold to the red area. The system is trained using U-Net semantic segmentation, where the input for the system consists of grayscale images and their corresponding masks. We utilize U-Net semantic segmentation to find the vulva in the input image, making it lightweight, simple, and robust enough to be tested on many images. To evaluate the performance of our model, we employ the intersection over union (IOU) metric, which is a suitable indicator for determining the model’s robustness. For the segmentation model, a prediction is generally considered ‘good’ when the intersection over union score surpasses 0.5. Our model achieved this criterion with a score of 0.58, surpassing the scores of alternative methods such as the SVM with Gabor (0.515) and YOLOv3 (0.52).

Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.

Early Blood-Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice.

Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood-brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.

Perturbations in risk/reward decision making and frontal cortical catecholamine regulation induced by mild traumatic brain injury

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and assessed for injury-induced effects on risk/reward decision making using a probabilistic discounting task (PDT). In the first week post-final surgery, mTBI increased risky choice preference. By the fourth week, males exhibited increased latencies to make risky choices following rmTBI, demonstrating a delayed effect on processing speed. When levels of tyrosine hydroxylase (TH) and the norepinephrine reuptake transporter (NET) were measured within subregions of the PFC, females exhibited dramatic increases of TH levels within the orbitofrontal cortex (OFC) following smTBI. However, both males and females demonstrated reduced levels of OFC NET following rmTBI. These results indicate the OFC is susceptible to catecholamine instability after rmTBI and suggests that not all areas of the PFC contribute equally to TBI-induced imbalances. Overall, the CH-CCI model of rmTBI has revealed time-dependent and sex-specific changes in risk/reward decision making and catecholamine regulation following repetitive mild head injuries.

A cross-sectional study to estimate the prevalence of text neck syndrome among medical students in a tertiary care teaching hospital in Andhra Pradesh

Abstract Background: The overuse of handheld mobile technology is leading to detrimental effects on the human body, one of which is text neck syndrome (TNS). This refers to neck pain and disability due to repetitive stress injury. Text neck can cause symptoms such as neck pain, shoulder pain, upper back pain, and increased curvature of spine. Objectives: The objective of this study was to estimate the prevalence, awareness, frequency, severity, and radiation of pain experienced by medical students and to determine the association between the duration of gadget usage and the severity of pain. Methodology: In this cross-sectional study, 1000 medical students were surveyed regarding the awareness and prevalence of TNS. The questionnaire consisted of 16 questions which included, demographic details and education details, and questions related to frequency, duration, purpose and time of usage, and position during use. Results: Out of 1000 students, 500 of the respondents did not know of TNS, 10 knew the term in detail, 160 were familiar with the term, and 330 had only heard of the term. The usage of electronic gadgets increased with age and was found statistically significant with P &lt; 0.05. A significant positive association (P &lt; 0.05) was found between the duration of usage of gadgets and the severity of pain. Conclusion: TNS is a real problem, and the students are not aware of the problem. The study showed that the longer the duration of gadget usage, the more adverse the symptoms.

176 Repetitive Traumatic Brain Injuries Are Associated With Poorer Outcomes at 1-Year and 3-7 Years After Index Injury

INTRODUCTION: Traumatic brain injury (TBI) patients are at risk for subsequent TBIs. Research on the longitudinal impact of repetitive TBI is limited. METHODS: The 18-center TRACK-TBI study enrolled subjects who presented to hospital and received head computed tomography (CT) within 24-hours of TBI between 2014-2018. Subjects were interviewed regarding post-index TBI during follow-up. Data from subjects aged = 17-years with 1-year or 3-7-year outcomes were extracted. Outcome measures included functional (GOSE:Glasgow Outcome Scale-Extended), post-concussive symptoms (PCS) (RPQ:Rivermead Post-Concussion Symptoms Questionnaire), psychological distress (BSI-18:Brief Symptom Inventory-18), depression (PHQ-9:Patient Health Questionnaire-9), post-traumatic stress disorder (PCL-5:PTSD-Checklist for DSM-5), and quality of life (QOL) (QOLIBRI-OS:Quality of Life After Brain Injury-Overall Scale). Multivariable regressions were adjusted for demographic, socioeconomic, and injury severity factors, and for multiple comparisons. Mean-differences (B), relative risks (RR), and 95% confidence intervals [CI] were reported. RESULTS: In 1,572 subjects, 3.2% and 12.2% sustained post-index TBI at 1-year and 3-7-years, respectively; 2.4% sustained multiple post-index TBIs at 3-7-years. Risk factors included psychiatric history, prior TBI, and extracranial injury severity. At 1-year, post-index TBI was independently associated with incomplete recovery (GOSE&lt;8; RR = 1.75 [1.04-2.94]), decreased QOL (QOLIBRI-OS: B = -15.9 [-22.6, -9.1]), and increased severity of PCS, psychological distress, PTSD, and depression (RPQ: B = 8.1 [4.2-11.9], BSI-18: B = 5.3 [2.1-8.6]; PCL-5: B = 7.8 [3.2-12.4]; PHQ-9: B = 3.0 [1.5-4.4]); effects were conserved at reduced magnitudes at 3-7-years. Multiple (=2 vs. 1) post-index TBIs were associated with greater symptom severities across all outcome measures. CONCLUSIONS: Post-index TBI is associated with incomplete functional recovery, increased PCS, psychological distress, PTSD, and depressive symptom severities, and decreased QOL at 1- and 3-7-years post-injury. Sustaining multiple post-index TBIs further increases symptom severity across all outcome domains. Institutional processes and resources for TBI prevention, education, counseling, and follow-up are greatly needed.

In vivo assessment of early effects of diamond-tipped microdermabrasion through the lens of line-field confocal optical coherence tomography.

Microdermabrasion is a cosmetic procedure that has gained popularity for skin rejuvenation by causing repetitive intraepidermal injury to stimulate the proliferation of fibroblasts and collagen production. Various clinical studies have demonstrated microdermabrasion's effectiveness in skin rejuvenation; however, most of these studies rely on clinical observation and scoring by observers rather than histologic or microscopic analysis. In our single-center prospective study, we used line-field confocal optical coherence tomography (LC-OCT), to non-invasively visualize the early effects of one microdermabrasion treatment on the facial epidermal and dermal structure. Using LC-OCT, this study aims to elucidate the microscopic and histological effects of microdermabrasion on epidermal and dermal structures, including epidermal thickness, as well as collagen and vascular patterns. Eight volunteers (Fitzpatrick skin types II-V) underwent one treatment of microdermabrasion. LC-OCT and VISIA imaging were performed before and 10 min after microdermabrasion, and at 48-h follow-up. Subjective evaluations of skin texture and adverse reactions were assessed 1 week posttreatment via a telephone call. Compared to LC-OCT images before treatment, images captured after one treatment of microdermabrasion showed a decrease in thickness and number of undulations in the stratum corneum. In the superficial dermis, enhancement in fibrillar collagen, as demonstrated by an increased prominence of crisscrossing hyper-refractile strands, was visualized. This was consistent with subjective and objective improvement in facial rhytids calculated by VISIA skin analysis. Treatment monitoring with LC-OCT demonstrated consistent histopathological changes with clinical visual improvement. Therefore, LC-OCT, has the potential to enable long-term histopathological monitoring of microdermabrasion and other cosmetic procedures without biopsy.

A Novel Experimental Approach for the Measurement of Vibration-Induced Changes in the Rheological Properties of Ex Vivo Ovine Brain Tissue.

Increased incidence of traumatic brain injury (TBI) imposes a growing need to understand the pathology of brain trauma. A correlation between the incidence of multiple brain traumas and rates of behavioural and cognitive deficiencies has been identified amongst people that experienced multiple TBI events. Mechanically, repetitive TBIs may affect brain tissue in a similar way to cyclic loading. Hence, the potential susceptibility of brain tissue to mechanical fatigue is of interest. Although temporal changes in ovine brain tissue viscoelasticity and biological fatigue of other tissues such as tendons and arteries have been investigated, no methodology currently exists to cyclically load ex vivo brain tissue. A novel rheology-based approach found a consistent, initial stiffening response of the brain tissue before a notable softening when subjected to a subsequential cyclic rotational shear. History dependence of the mechanical properties of brain tissue indicates susceptibility to mechanical fatigue. Results from this investigation increase understanding of the fatigue properties of brain tissue and could be used to strengthen therapy and prevention of TBI, or computational models of repetitive head injuries.

Return to Play in Youth Athletes: Role of the Radiologist with Focus on the Upper Extremity.

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play.

Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury.

The repositioning of previously approved drugs is occupying the researchers' plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. A (23) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula's efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology. The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.

Repetitive traumatic brain injury-induced complement C1-related inflammation impairs long-term hippocampal neurogenesis.

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/β-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Abstract 2149 Cell-specific differential gene expression analysis by snRNA-seq after repetitive weaponry-type blast-induced traumatic brain injury

Abstract 2149 Cell-specific differential gene expression analysis by snRNA-seq after repetitive weaponry-type blast-induced traumatic brain injury

Repetitive head injuries in German American football players do not change blood-based biomarker candidates for CTE during a single season

BackgroundRepetitive traumatic brain injuries in American football players (AFPs) can lead to the neurodegenerative disease chronic traumatic encephalopathy (CTE). Clinical symptoms of CTE range from mood and behavioral changes to cognitive impairment, depression, and suicidality. So far, CTE cannot be diagnosed in vivo and thus specific diagnostic parameters for CTE need to be found, to observe and treat exposed athletes as early as possible. Promising blood-based biomarkers for CTE include total tau (tTau), hyperphosphorylated tau (pTau), neurofilament light protein (NF-L), glial fibrillary acidic protein (GFAP), amyloid-β40 (Aβ40), amyloid-β42 (Aβ42) and calcium-binding protein B (S100-B). Previous studies have found elevated levels of these biomarkers in subjects exposed to TBIs, whereas cerebrospinal fluid (CSF) levels of Aβ40 and Aβ42 were decreased in CTE subjects. Here, we investigated whether young AFPs already exhibit changes of these biomarker candidates during the course of a single active season.MethodsBlood samples were drawn from n = 18 American Football Players before and after a full season and n = 18 male age-matched control subjects. The plasma titers of tTau, pTau, NF-L, GFAP, Aβ40, Aβ42 and S100-B were determined. Additionally, Apathy, Depression, and Health status as well as the concussion history and medical care were assessed and analyzed for correlations.ResultsHere we show, that the selected biomarker candidates for CTE do not change significantly during the seven-month period of a single active season of American Football in blood samples of AFPs compared to healthy controls. But interestingly, they exhibit generally elevated pTau titers. Furthermore, we found correlations of depression, quality-of-life, career length, training participation and training continuation with headache after concussion with various titers.ConclusionOur data indicates, that changes of CTE marker candidates either occur slowly over several active seasons of American Football or are exclusively found in CSF. Nevertheless, our results underline the importance of a long-term assessment of these biomarker candidates, which might be possible through repeated blood biomarker monitoring in exposed athletes in the future.