Search Results (18)

Traumatic brain injury (TBI) remains a significant public health concern, particularly among military personnel and contact sport athletes who are frequently exposed to repeated blast overpressure waves and mild concussive impacts, respectively. While moderate and severe TBIs have been extensively studied, the long-term neuroendocrine consequences of mild, repetitive brain trauma are poorly understood. In this study, we investigated the temporal dynamics of hypothalamic–pituitary–adrenal (HPA) axis dysregulation following repeated mild concussive head impacts and blast exposures using two clinically relevant rodent models. Male Sprague-Dawley rats were subjected to repeated mild concussive impacts using a modified weight drop model or repeated blast exposures using an advanced blast simulator. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured on days 1 and 30 post-injuries. Our findings revealed that repeated blast exposures induced elevation of plasma ACTH and corticosterone on days 1 and 30 post-blasts. After the repeated mild concussive impacts, increased plasma levels of corticosterone were observed on days 1 and 30, but ACTH levels were increased only on day 30. This study is among the first to directly compare neuroendocrine outcomes of repeated mild concussive impacts and blast exposures within a unified experimental framework. Our findings demonstrate distinct temporal trajectories of HPA axis dysregulation depending on injury type and highlight plasma levels of ACTH and corticosterone as potential biomarkers of subclinical brain trauma. These insights may inform early diagnostic approaches and therapeutic strategies aimed at mitigating long-term stress-related complications following mild traumatic brain injuries. Full article

Background/Objectives: Suicides among U.S. military veterans are alarmingly high, driven by factors such as mental health issues, combat exposure, and history of mild traumatic brain injury (mTBI)/concussion. This study aims to examine the relationship between concussion history, combat experience, and their effects on mental health issues and suicide ideation among military veterans. Additionally, this study investigates the impact of post-traumatic stress disorder (PTSD) on these variables. Methods: A total of 78 veterans (62 males, 16 females) participated in this study. Participants completed a demographic survey and the Global Well-being Index (GWI) to assess concussion history and residual symptoms. A licensed social worker interviewed the veterans using the 9-Item Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder survey (7 Items) (GAD-7) for anxiety, and the Columbia-Suicide Severity Rating Scale (C-SSRS) for suicide ideation. A 2 × 2 cross-tabulation analysis examined the relationships between concussion history, combat experience, and outcomes of anxiety, depression, and suicide ideation. PTSD was also assessed as both a predictor and an outcome. Statistical analyses yielded odds ratios (OR) with 95% confidence intervals (CI), Chi-square, and Cramer’s V (V) correlations along with associated p-values. Results: The combination of concussion history and combat experience strongly predicted either anxiety, depression, or suicide ideation (OR = 7.97, 95% CI: 1.70, 37.44; V = 0.334, (p = 0.003)), more than either factor alone. Combat experience was the strongest predictor of PTSD (OR = 11.12, 95% CI: 3.30, 37.47; V = 0.485, p ≤ 0.001), both individually and when combined with concussion history. PTSD strongly influenced mental health issues and suicide ideation (OR = 8.16, 95% CI: 1.74, 38.25; V = 0.339, p = 0.003). Stratification by PTSD status (positive or negative) affected the relationships between independent and dependent variables. Small cell counts resulted in a wide 95% CI for some ORs, though some statistically significant Fisher’s Exact Test results were observed. Credibility analysis using the critical prior interval (CPI) metric confirmed the intrinsic credibility of the results. Conclusions: This study provides insights into the relationships between concussion history, combat experience, and their impacts on mental health issues and suicide ideation among military veterans. Full article

Finding an effective treatment for traumatic brain injury is challenging for multiple reasons. There are innumerable different causes and resulting levels of damage for both penetrating and non-penetrating traumatic brain injury each of which shows diverse pathophysiological progressions. More concerning is that disease progression can take decades before neurological symptoms become obvious. Currently, the primary treatment for non-penetrating mild traumatic brain injury, also called concussion, is bed rest despite the fact the majority of emergency room visits for traumatic brain injury are due to this mild form. Furthermore, one-third of mild traumatic brain injury cases progress to long-term serious symptoms. This argues for the earliest therapeutic intervention for all mild traumatic brain injury cases which is the focus of this review. Calcium levels are greatly increased in damaged brain regions as a result of the initial impact due to tissue damage as well as disrupted ion channels. The dysregulated calcium level feedback is a diversity of ways to further augment calcium neurotoxicity. This suggests that targeting calcium levels and function would be a strong therapeutic approach. An effective calcium-based traumatic brain injury therapy could best be developed through therapeutic programs organized in professional team sports where mild traumatic brain injury events are common, large numbers of subjects are involved and professional personnel are available to oversee treatment and documentation. This review concludes with a proposal with that focus. Full article

Introduction: Concussion is known to cause transient autonomic and cerebrovascular dysregulation that generally recovers; however, few studies have focused on individuals with an extensive concussion history. Method: The case was a 26-year-old male with a history of 10 concussions, diagnosed for bipolar type II disorder, mild attention-deficit hyperactivity disorder, and a history of migraines/headaches. The case was medicated with Valproic Acid and Escitalopram. Sensor-based baseline data were collected within six months of his injury and on days 1–5, 10, and 14 post-injury. Symptom reporting, heart rate variability (HRV), neurovascular coupling (NVC), and dynamic cerebral autoregulation (dCA) assessments were completed using numerous biomedical devices (i.e., transcranial Doppler ultrasound, 3-lead electrocardiography, finger photoplethysmography). Results: Total symptom and symptom severity scores were higher for the first-week post-injury, with physical and emotional symptoms being the most impacted. The NVC response showed lowered activation in the first three days post-injury, while autonomic (HRV) and autoregulation (dCA) were impaired across all testing visits occurring in the first 14 days following his concussion. Conclusions: Despite symptom resolution, the case demonstrated ongoing autonomic and autoregulatory dysfunction. Larger samples examining individuals with an extensive history of concussion are warranted to understand the chronic physiological changes that occur following cumulative concussions through biosensing devices. Full article

Concussions, a prevalent public health concern in the United States, often result from mild traumatic brain injuries (mTBI), notably in sports such as American football. There is limited exploration of smart-textile-based sensors for measuring the head impacts associated with concussions in sports and recreational activities. In this paper, we describe the development and construction of a smart textile impact sensor (STIS) and validate STIS functionality under high magnitude impacts. This STIS can be inserted into helmet cushioning to determine head impact force. The designed 2 × 2 STIS matrix is composed of a number of material layered structures, with a sensing surface made of semiconducting polymer composite (SPC). The SPC dimension was modified in the design iteration to increase sensor range, responsiveness, and linearity. This was to be applicable in high impact situations. A microcontroller board with a biasing circuit was used to interface the STIS and read the sensor’s response. A pendulum test setup was constructed to evaluate various STISs with impact forces. A camera and Tracker software were used to monitor the pendulum swing. The impact forces were calculated by measuring the pendulum bob’s velocity and acceleration. The performance of the various STISs was measured in terms of voltage due to impact force, with forces varying from 180 to 722 N. Through data analysis, the threshold impact forces in the linear range were determined. Through an analysis of linear regression, the sensors’ sensitivity was assessed. Also, a simplified model was developed to measure the force distribution in the 2 × 2 STIS areas from the measured voltages. The results showed that improving the SPC thickness could obtain improved sensor behavior. However, for impacts that exceeded the threshold, the suggested sensor did not respond by reflecting the actual impact forces, but it gave helpful information about the impact distribution on the sensor regardless of the accurate expected linear response. Results showed that the proposed STIS performs satisfactorily within a range and has the potential to be used in the development of an e-helmet with a large STIS matrix that could cover the whole head within the e-helmet. This work also encourages future research, especially on the structure of the sensor that could withstand impacts which in turn could improve the overall range and performance and would accurately measure the impact in concussion-causing impact ranges. Full article

Post-traumatic headache (PTH) is a common and debilitating consequence of mild traumatic brain injury (mTBI) that can occur over one year after the head impact event. Thus, better understanding of the underlying pathophysiology and risk factors could facilitate early identification and management of PTH. There are several factors that could influence the reporting of PTH prevalence, including the definition of concussion and PTH. The main risk factors for PTHs include a history of migraines or headaches, female gender, younger age, greater severity of the head injury, and co-occurring psychological symptoms, such as anxiety and depression. PTH clinical profiles vary based on onset, duration, and severity: tension-type headache, migraine headaches, cervicogenic headache, occipital neuralgia, and new daily persistent headache. Pharmacological treatments often consist of analgesics and non-steroidal anti-inflammatory drugs, tricyclic antidepressants, or antiepileptic medication. Cognitive behavioral therapy, relaxation techniques, biofeedback, and physical therapy could also be used for PTH treatment. Our work highlighted the need for more rigorous studies to better describe the importance of identifying risk factors and patient-centered treatments and to evaluate the effectiveness of the existing treatment options. Clinicians should consider a multidisciplinary approach to managing PTH, including pharmacotherapy, cognitive behavioral therapy, and lifestyle changes. Full article

Traumatic brain injury (TBI) is a major cause of death and disability and is experienced by nearly 3 million people annually as a result of falls, vehicular accidents, or from being struck by or against an object. While TBIs can range in severity, the majority of injuries are considered to be mild. However, TBI of any severity has the potential to have long-lasting neurological effects, including headaches, cognitive/memory impairments, mood dysfunction, and fatigue as a result of neural damage and neuroinflammation. Here, we modified a projectile concussive impact (PCI) model of TBI to deliver a closed-head impact with variable severity dependent on the material of the ball-bearing projectile. Adult male Sprague Dawley rats were evaluated for neurobehavioral, neuroinflammatory, and neural damage endpoints both acutely and longer-term (up to 72 h) post-TBI following impact with either an aluminum or stainless-steel projectile. Animals that received TBI using the stainless-steel projectile exhibited outcomes strongly correlated to moderate-severe TBI, such as prolonged unconsciousness, impaired neurobehavior, increased risk for hematoma and death, as well as significant neuronal degeneration and neuroinflammation throughout the cortex, hippocampus, thalamus, and cerebellum. In contrast, rats that received TBI with the aluminum projectile exhibited characteristics more congruous with mild TBI, such as a trend for longer periods of unconsciousness in the absence of neurobehavioral deficits, a lack of neurodegeneration, and mild neuroinflammation. Moreover, alignment of cytokine mRNA expression from the cortex of these rats with a computational model of neuron–glia interaction found that the moderate-severe TBI produced by the stainless-steel projectile strongly associated with the neuroinflammatory state, while the mild TBI existed in a state between normal and inflammatory neuron–glia interactions. Thus, these modified PCI protocols are capable of producing TBIs that model the clinical and experimental manifestations associated with both moderate-severe and mild TBI producing relevant models for the evaluation of the potential underlying roles of neuroinflammation and other chronic pathophysiology in the long-term outcomes associated with TBI. Full article

Objective: To understand the methodological approaches taken by various research groups and determine the kinematic variables that could consistently and reliably differentiate between concussed and non-concussed individuals. Methods: MEDLINE via PubMed, CINAHL Complete via EBSCO, EBSCOhost, SPORTDiscus, and Scopus were searched from inception until 31 December 2021, using key terms related to concussion, mild traumatic brain injury, gait, cognition and dual task. Studies that reported spatiotemporal kinematic outcomes were included. Data were extracted using a customised spreadsheet, including detailed information on participant characteristics, assessment protocols, equipment used, and outcomes. Results: Twenty-three studies involving 1030 participants met the inclusion criteria. Ten outcome measures were reported across these articles. Some metrics such as gait velocity and stride length may be promising but are limited by the status of the current research; the majority of the reported variables were not sensitive enough across technologies to consistently differentiate between concussed and non-concussed individuals. Understanding variable sensitivity was made more difficult given the absence of any reporting of reliability of the protocols and variables in the respective studies. Conclusion: Given the current status of the literature and the methodologies reviewed, there would seem little consensus on which gait parameters are best to determine return to play readiness after concussion. There is potential in this area for such technologies and protocols to be utilised as a tool for identifying and monitoring concussion; however, improving understanding of the variability and validity of technologies and protocols underpins the suggested directions of future research. Inertial measurement units appear to be the most promising technology in this aspect and should guide the focus of future research. Impact: Results of this study may have an impact on what technology is chosen and may be utilised to assist with concussion diagnosis and return to play protocols. Full article

College-aged individuals with anxiety are vulnerable to developing persistent concussion symptoms, yet evidence-based treatments for this population are limited. Understanding these individuals’ perspectives is critical for developing effective interventions. We conducted qualitative interviews with 17 college-aged individuals (18–24 years old) with a recent (≤10 weeks) concussion and at least mild anxiety (≥5 on the GAD-7 questionnaire) to understand the life impact of their concussion. We identified 5 themes: (1) disruption to daily activities (e.g., reduced participation in hobbies and physical activity); (2) disruption to relationships (e.g., reduced social engagement, feeling dismissed by others, stigma, and interpersonal friction); (3) disruptions in school/work (e.g., challenges participating due to light sensitivity, cognitive or sleep disturbance, and related emotional distress); (4) changes in view of the self (e.g., feeling “unlike oneself”, duller, or more irritable), and (5) finding “silver linings” after the injury (e.g., increased motivation). Concussions impact the lives of college-aged individuals with co-occurring anxiety in a broad range of domains, many of which remain largely neglected in standard concussion clinical assessment and treatment. Assessing and addressing these issues has the potential to limit the negative impact of concussion, promote recovery, and potentially help prevent persistent concussion symptoms in this at-risk population. Full article

(1) Background: Cerebral autoregulation is altered during acute mild traumatic brain injury, or concussion. However, it is unknown how a history of concussion can impact cerebral haemodynamic activity during a task that elicits an autoregulatory response. (2) Methods: We assessed cerebral haemodynamic activity in those with a history of three or more concussions. The study included 44 retired athletes with concussion history and 25 control participants. We recorded participants’ relative changes in right and left pre-frontal cortex oxygenation collected by near-infrared spectroscopy and continuous beat-to-beat blood pressure measured by finger photoplethysmography. Participants completed a 5-min seated rest followed by a 5-min repeated squat (10-s) stand (10-s) maneuver (0.05 Hz) to elicit a cerebral autoregulatory response. Wavelet transformation was applied to the collected signals, allowing separation into cardiac interval I (0.6 to 2 Hz), respiratory interval II (0.145 to 0.6 Hz), and smooth muscle cell interval III (0.052 to 0.145 Hz). (3) Results: Significant increases at cardiac interval I were found for the wavelet amplitude of oxy-haemoglobin and haemoglobin difference at the right pre-frontal cortex. No significant difference was found at the left pre-frontal cortex or the blood pressure wavelet amplitudes. (4) Conclusions: Contributions from cardiac activity to the pre-frontal cortex oxygenation are elevated when eliciting dynamic cerebral autoregulation in those with a history of three or more concussions. Full article

Epidemiological studies of the neurological health of former professional soccer players are being undertaken to identify whether heading the ball is a risk factor for disease or premature death. A quantitative estimate of exposure to repeated sub-concussive head impacts would provide an opportunity to investigate possible exposure-response relationships. However, it is unclear how to formulate an appropriate exposure metric within the context of epidemiological studies. We have carried out a systematic review of the scientific literature to identify the factors that determine the magnitude of head impact acceleration during experiments and from observations during playing or training for soccer, up to the end of November 2021. Data were extracted from 33 experimental and 27 observational studies from male and female amateur players including both adults and children. There was a high correlation between peak linear and angular accelerations in the observational studies (p < 0.001) although the correlation was lower for the experimental data. We chose to rely on an analysis of maximum or peak linear acceleration for this review. Differences in measurement methodology were identified as important determinants of measured acceleration, and we concluded that only data from accelerometers fixed to the head provided reliable information about the magnitude of head acceleration from soccer-related impacts. Exposures differed between men and women and between children and adults, with women on average experiencing higher acceleration but less frequent impacts. Playing position appears to have some influence on the number of heading impacts but less so on the magnitude of the head acceleration. Head-to-head collisions result in high levels of exposure and thus probably risk causing a concussion. We concluded, in the absence of evidence to the contrary, that estimates of the cumulative number of heading impacts over a playing career should be used as the main exposure metric in epidemiological studies of professional players. Full article

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion. Full article

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury. Full article

Repetitive mild traumatic brain injuries (mTBIs) contribute to inflammation-induced neurodegeneration. Cycloxygenase (COX) enzymes produce inflammatory cytokines that influence the microglia response to neurotrauma. Celecoxib is a selective COX-2 inhibitor that is prescribed in some conditions of mTBI to alleviate symptoms of concussion, and has shown benefits in neurodegenerative conditions. We investigated molecular pathways of neuroinflammation in response to celecoxib treatment in a mouse model of repetetive mTBI. Fifteen mTBIs were delivered over 23 days in adult male C57BL/6J mice in one of four groups (control, celecoxib without impact, celecoxib with impact, and vehicle with impact). Cognitive function was assessed at 48 h and three months following the final mTBI. Morris Water Maze testing revealed impaired hippocampal spatial learning performance in the celecoxib treatment with the impact group compared to the vehicle with impact control in the acute phase, with celecoxib treatment providing no improvement compared with the control at chronic testing; mRNA analysis of the cerebral cortex and hippocampus revealed expression change, indicating significant improvement in microglial activation, inflammation, excitotoxicity, and neurodegeneration at chronic measurement. These data suggest that, in the acute phase following injury, celecoxib protected against neuroinflammation, but exacerbated clinical cognitive disturbance. Moreover, while there was evidence of neuroprotective alleviation of mTBI pathophysiology at chronic measurement, there remained no change in clinical features. Full article

Sport-related traumatic brain injury (TBI) elicits a multifaceted inflammatory response leading to brain injury and morbidity. This response could be a predictive tool for the progression of TBI and to stratify the injury of which mild TBI is most prevalent. Therefore, we examined the differential expression of serum inflammatory markers overtime and identified novel markers in repetitively concussed athletes. Neuropsychological assessment by Wechsler Adult Intelligence Scale (WAIS) and Immediate Post Concussion Assessment and Cognitive Test (ImPACT) was performed on rugby players and serum was taken from healthy, concussed and repetitively concussed athletes. Serum was also obtained <1 week and >1 week after trauma and analyzed for 92 inflammatory protein markers. Fibroblast growth factor 21 (FGF21) and interleukin-7 (IL-7) differentiated repetitively concussed athletes. Macrophage chemotactic protein-1 (MCP-1), tumor necrosis factor superfamily member 14 (TNFSF14) were significantly reduced >1 week and chemokine (C-X3-C motif) ligand 1 (CX3CL1) upregulated <1 week after injury. FGF21 and MCP-1 negatively correlated with symptoms and their severity. We have identified dynamic changes in the inflammatory response overtime and in different classes of concussion correlating with disease progression. This data supports the use of inflammatory biomarkers as predictors of symptom development due to secondary complications of sport-related mTBI. Full article