ω-3 fatty acid supplementation as a potential therapeutic aid for the recovery from mild traumatic brain injury/concussion.
ABSTRACT: Sports-related concussions or mild traumatic brain injuries (mTBIs) are becoming increasingly recognized as a major public health concern; however, no effective therapy for these injuries is currently available. ω-3 (n-3) fatty acids, such as docosahexaenoic acid (DHA), have important structural and functional roles in the brain, with established clinical benefits for supporting brain development and cognitive function throughout life. Consistent with these critical roles of DHA in the brain, accumulating evidence suggests that DHA may act as a promising recovery aid, or possibly as a prophylactic nutritional measure, for mTBI. Preclinical investigations demonstrate that dietary consumption of DHA provided either before or after mTBI improves functional outcomes, such as spatial learning and memory. Mechanistic investigations suggest that DHA influences multiple aspects of the pathologic molecular signaling cascade that occurs after mTBI. This review examines the evidence of interactions between DHA and concussion and discusses potential mechanisms by which DHA helps the brain to recover from injury. Additional clinical research in humans is needed to confirm the promising results reported in the preclinical literature.
Project description:Impulsivity and poor executive control have been implicated in the pathogenesis of many developmental and neuropsychiatric disorders. Similarly, concussions/mild traumatic brain injuries (mTBI) have been associated with increased risk for neuropsychiatric disorders and the development of impulsivity and inattention. Researchers and epidemiologists have therefore considered whether or not concussions induce symptoms of attention-deficit/hyperactivity disorder (ADHD), or merely unmask impulsive tendencies that were already present. The purpose of this study was to determine if a single concussion in adolescence could induce ADHD-like impulsivity and impaired response inhibition, and subsequently determine if inherent impulsivity prior to a pediatric mTBI would exacerbate post-concussion symptomology with a specific emphasis on impulsive and inattentive behaviours. As these behaviours are believed to be associated with the frontostriatal circuit involving the nucleus accumbens (NAc) and the prefrontal cortex (PFC), the expression patterns of 8 genes (Comt, Drd2, Drd3, Drd4, Maoa, Sert, Tph1, and Tph2) from these two regions were examined. In addition, Golgi-Cox staining of medium spiny neurons in the NAc provided a neuroanatomical examination of mTBI-induced structural changes. The study found that a single early brain injury could induce impulsivity and impairments in response inhibition that were more pronounced in males. Interestingly, when animals with inherent impulsivity experienced mTBI, injury-related deficits were exacerbated in female animals. The single concussion increased dendritic branching, but reduced synaptic density in the NAc, and these changes were likely associated with the increase in impulsivity. Finally, mTBI-induced impulsivity was associated with modifications to gene expression that differed dramatically from the gene expression pattern associated with inherent impulsivity, despite very similar behavioural phenotypes. Our findings suggest the need to tailor treatment strategies for mTBI in light of an individual's premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype.
Project description:Mild traumatic brain injuries (mTBIs) are often associated with posttraumatic stress disorder (PTSD). In cases of chronic mTBI, accurate diagnosis can be challenging due to the overlapping symptoms this condition shares with PTSD. Furthermore, mTBIs are heterogeneous and not easily observed using conventional neuroimaging tools, despite the fact that diffuse axonal injuries are the most common injury. Diffusion tensor imaging (DTI) is sensitive to diffuse axonal injuries and is thus more likely to detect mTBIs, especially when analyses account for the inter-individual variability of these injuries. Using a subject-specific approach, we compared fractional anisotropy (FA) abnormalities between groups with a history of mTBI (n = 35), comorbid mTBI and PTSD (mTBI + PTSD; n = 22), and healthy controls (n = 37). We compared all three groups on the number of abnormal FA clusters derived from subject-specific injury profiles (i.e., individual z-score maps) along a common white matter skeleton. The mTBI + PTSD group evinced a greater number of abnormally low FA clusters relative to both the healthy controls and the mTBI group without PTSD (p < .05). Across the groups with a history of mTBI, increased numbers of abnormally low FA clusters were significantly associated with PTSD symptom severity, depression, post-concussion symptoms, and reduced information processing speed (p < .05). These findings highlight the utility of subject-specific microstructural analyses when searching for mTBI-related brain abnormalities, particularly in patients with PTSD. This study also suggests that patients with a history of mTBI and comorbid PTSD, relative to those without PTSD, are at increased risk of FA abnormalities.
Project description:Concussions have been associated with elevated musculoskeletal injury risk; however, the influence of unreported and unrecognized concussions has not been investigated.The purpose of this study was to examine the association between concussion and lower extremity musculoskeletal injury rates across a diverse array of sports among collegiate student-athletes at the conclusion of their athletic career. The hypothesis was that there will be a positive association between athletes who reported a history of concussions and higher rates of lower extremity injuries.Cross-sectional study.Level 3.Student-athletes (N = 335; 62.1% women; mean age, 21.2 ± 1.4 years) from 13 sports completed a reliable injury history questionnaire. Respondents indicated the total number of reported, unreported, and potentially unrecognized concussions as well as lower extremity injuries including ankle sprains, knee injuries, and muscle strains. Chi-square analyses were performed to identify the association between concussion and lower extremity injuries.There were significant associations between concussion and lateral ankle sprain ( P = 0.012), knee injury ( P = 0.002), and lower extremity muscle strain ( P = 0.031). There were also significant associations between reported concussions and knee injury ( P = 0.003), unreported concussions and knee injury ( P = 0.002), and unrecognized concussions and lateral ankle sprain ( P = 0.001) and lower extremity muscle strains ( P = 0.006), with odds ratios ranging from 1.6 to 2.9.There was a positive association between concussion history and lower extremity injuries (odds ratios, 1.6-2.9 elevated risk) among student-athletes at the conclusion of their intercollegiate athletic careers.Clinicians should be aware of these elevated risks when making return-to-participation decisions and should incorporate injury prevention protocols.
Project description:OBJECTIVE:Concussions are the most frequent traumatic brain injuries. Yet, the socioeconomic impact of concussions remains unclear. Socioeconomic effects of concussions on working-age adults were studied on a population scale. DESIGN:This population-based, event time study uses administrative data as well as hospital and emergency room records for the population of Denmark. SETTING:We study all Danish patients, aged 20-59 years, who were treated at a public hospital or at an emergency room between 2003 and 2017 after suffering a concussion without other intracranial or extracranial injuries (n=55 424 unique individuals). None of the patients had a prior diagnosis of intracranial or extracranial injuries within the past 10 years leading up to the incident. PRIMARY AND SECONDARY OUTCOME MEASURES:As primary endpoint, we investigate the mean effect of concussion on annual salaried income within a 5-year period after trauma. In an exploratory analysis, we study whether the potential impact of concussion on annual salaried income is driven by patient age, education or economic cycle. RESULTS:Concussion was associated with an average change in annual salary income of -€1223 (95% CI: -€1540 to -905, p<0.001) corresponding to a salary change of -4.2% (95% CI: -5.2% to -3.1 %). People between 30 and 39 years and those without high school degrees suffered the largest salary decreases. Affected individuals leaving the workforce drove the main part of the decrease. Absolute annual effect sizes were countercyclical to the unemployment rate. CONCLUSIONS:Concussions have a large and long-lasting impact on salary and employment of working-age adults on a nationwide scale.
Project description:Mild traumatic brain injury (mTBI) is increasingly recognized as a significant public health problem which warrants additional research. Part of the effort to understand mTBI and concussion includes modeling in animals. Controlled cortical impact (CCI) is a commonly employed and well-characterized model of experimental TBI that has been utilized for three decades. Today, several commercially available pneumatic- and electromagnetic-CCI devices exist as do a variety of standard and custom injury induction tips. One of CCI's strengths is that it can be scaled to a number of common laboratory animals. Similarly, the CCI model can be used to produce graded TBI ranging from mild to severe. At the mild end of the injury spectrum, CCI has been applied in many ways, including to study open and closed head mTBI, repeated injuries, and the long-term deficits associated with mTBI and concussion. The purpose of this mini-review is to introduce the CCI model, discuss ways the model can be applied to study mTBI and concussion, and compare CCI to alternative pre-clinical TBI models.
Project description:<h4>Background</h4>Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community.<h4>Methods</h4>We performed a longitudinal cohort analysis of adults with diagnosis of a concussion in Ontario, Canada, from Apr. 1, 1992, to Mar. 31, 2012 (a 20-yr period), excluding severe cases that resulted in hospital admission. The primary outcome was the long-term risk of suicide after a weekend or weekday concussion.<h4>Results</h4>We identified 235,110 patients with a concussion. Their mean age was 41 years, 52% were men, and most (86%) lived in an urban location. A total of 667 subsequent suicides occurred over a median follow-up of 9.3 years, equivalent to 31 deaths per 100,000 patients annually or 3 times the population norm. Weekend concussions were associated with a one-third further increased risk of suicide compared with weekday concussions (relative risk 1.36, 95% confidence interval 1.14-1.64). The increased risk applied regardless of patients' demographic characteristics, was independent of past psychiatric conditions, became accentuated with time and exceeded the risk among military personnel. Half of these patients had visited a physician in the last week of life.<h4>Interpretation</h4>Adults with a diagnosis of concussion had an increased long-term risk of suicide, particularly after concussions on weekends. Greater attention to the long-term care of patients after a concussion in the community might save lives because deaths from suicide can be prevented.
Project description:OBJECTIVE:To determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS. METHODS:One hundred and ten children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children's Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI subdomain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks postinjury and 8-10 weeks postinjury. Gray matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry at 4 weeks postinjury. Functional connectivity was estimated at the same timepoint using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of gray matter and functional connectivity indices carried meaningful prognostic information. RESULTS:Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in gray matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep-related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow-up (area under the curve = 0.86). INTERPRETATION:These results highlight that the function-structure profile of core default mode regions underpins sleep-related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.
Project description:BACKGROUND:Mild traumatic brain injury (MTBI) represents 70-80% of all treated brain injuries. A considerable proportion of MTBI patients experience post-concussion symptoms for a prolonged period after MTBI, and these symptoms are diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a range of physical, cognitive, and emotional symptoms. However, memory and executive dysfunction seems to be one of the most debilitating symptoms. Recently, non-invasive brain stimulation has been studied as a potential treatment method for traumatic brain injury (TBI) patients. Therefore, our primary goal is to verify the effects of transcranial direct current stimulation (tDCS) in patients with PPCS who demonstrate cognitive deficits in long-term episodic memory, working memory, and executive function following MTBI. METHODS/DESIGN:This is a randomized crossover trial of patients with a history of MTBI with cognitive deficits in memory and executive function. Thirty adult patients will be randomized in a crossover manner to receive three weekly sessions of anodal tDCS (2?mA) at left dorsolateral prefrontal cortex, left temporal cortex, and sham stimulation that will be performed at 7-day intervals (washout period). The clinical diagnosis of PPCS will be determined using the Rivermead Post-Concussion Symptoms Questionnaire. Patients who meet the inclusion criteria will be assessed with a neuropsychological evaluation. A new battery of computerized neuropsychological tests will be performed before and immediately after each stimulation. Statistical analysis will be performed to determine trends of cognitive improvement. DISCUSSION:There is paucity of studies regarding the use of tDCS in TBI patients, and although recent results showed controversial data regarding the effects of tDCS in such patients, we will address specifically patients with PPCS and MTBI and no brain abnormalities on CT scan other than subarachnoid hemorrhage. Moreover, due to the missing information on literature regarding the best brain region to be studied, we will evaluate two different regions to find immediate effects of tDCS on memory and executive dysfunction. CLINICAL TRIAL REGISTRATION:www.ClinicalTrials.gov, identifier NCT02292589 (https://register.clinicaltrials.gov).
Project description:Collision sports, such as Rugby Union (“Rugby”) have a particularly high risk of injury. Of all injuries common to collision sports, concussions have received the most attention due to the potentially negative cognitive effects in the short- and long-term. Despite non-professional Rugby players comprising the majority of the world’s playing population, there is relatively little research in this population. Stellenbosch Rugby Football Club (“Maties”), the official rugby club of Stellenbosch University, represents one of the world’s largest non-professional Rugby clubs, making this an ideal cohort for community-level injury surveillance. The aim of this study was to describe the incidence and events associated with concussion in this cohort. Baseline demographics were obtained on the 807 male student Rugby non-professional players who registered for the 10-week long 2018 season, which comprised 101 matches and 2,915 of exposure hours. All match-related injuries were captured by the medical staff of Stellenbosch Campus Health Service on an electronic form developed from the consensus statement for injury recording in Rugby. The mean age, height and weight of this cohort were 20 ± 2 years, 182 ± 7 cm and 88 ± 14 kg, respectively. Overall, there were 89 time-loss injuries, which equated to an injury rate of 30.6 per 1,000 match hours [95% confidence intervals (CIs): 24.2–36.9], or about one injury per match. The most common injury diagnosis was “concussion” (n = 27 out of 90 injuries, 30%), at a rate of 9.3 per 1,000 match hours (95% CIs: 5.8–12.8). The three most common mechanisms of concussion in the present study were performing a tackle (33%), accidental collision (30%) and being tackled (11%). Concussion was the most common injury in this population, at a rate that was six times higher than the most comparable study from the UK, which had far more exposure time over six seasons and wider range of player ability, from recreational to semi-professional. This might be explained by the training and vigilance of the club’s first aiders observing all matches for concussion. Future studies should try to explain this high rate and subsequently reduce these concussions. The addition of video surveillance data would assist in identifying the etiology of these concussions injuries in order to develop specific targeted interventions.
Project description:PURPOSE OF REVIEW:The concussion public health burden has increased alongside our knowledge of the pathophysiology of mild traumatic brain injury (mTBI). The purpose of this review is to summarize our current understanding of mTBI pathophysiology and biomechanics and how these underlying principles correlate with clinical manifestations of mTBI. RECENT FINDINGS:Changes in post-mTBI glutamate and GABA concentrations seem to be region-specific and time-dependent. Genetic variability may predict recovery and symptom severity while gender differences appear to be associated with the neuroinflammatory response and neuroplasticity. Ongoing biomechanical research has shown a growing body of evidence in support of an "individual-specific threshold" for mTBI that varies based on individual intrinsic factors. The literature demonstrates a well-characterized timeframe for mTBI pathophysiologic changes in animal models while work in this area continues to grow in humans. Current human research shows that these underlying post-mTBI effects are multifactorial and may correlate with symptomatology and recovery. While wearable sensor technology has advanced biomechanical impact research, a definitive concussion threshold remains elusive.