Journal of neurotrauma最新文献

Traumatic brain injury (TBI) is a major health problem worldwide. Approximately 2.8 million people in the United States sustain a TBI each year, the majority of which can be classified as mild TBI (mTBI) or concussive injuries. Although mTBI may not cause overt brain damage, it triggers many cellular and molecular changes in brain cells, resulting in neurological, cognitive, and behavioral impairments. Metabolites are released in response to mTBI and can serve as diagnostic markers, as well as potentially contributing to ongoing pathophysiological changes. N-formylmethionine (fMet) is used as the first amino acid for protein synthesis in mitochondria, bacteria, and chloroplasts. Both formylated peptides and free fMet have been detected in human plasma. While a number of studies have demonstrated that formylated peptides can activate the innate immune response, less is known about the role of free fMet in health and disease. In this study, we quantified the free fMet concentration in plasma samples obtained from persons who have sustained an mTBI and compared it with the plasma concentrations detected in healthy volunteers. Our results show that the plasma levels of fMet increased within 24 h of a documented mTBI in both males and females. Receiver operator characteristic (ROC) analysis indicated that the acute change in plasma fMet (<48 h after an injury) has an area under ROC (AUROC) of 0.82 in identifying an mTBI. Interestingly, when fMet was measured in plasma samples collected from these patients 3 months later, it remained elevated and had an AUROC of 0.88. The systemic administration of fMet to mTBI mice impaired brain mitochondrial function, suggesting that it may affect ongoing mTBI pathophysiology.

The family environment plays an important role in children's recovery from traumatic brain injury (TBI); however, parental and family factors have not been examined in-depth in pediatric mild TBI (mTBI). Existing research on postconcussive symptoms (PCS) typically employs conventional statistical analyses that assume that children with mTBI are a homogenous group. However, children may display distinct trajectories of PCS across time after mTBI. Group-based multitrajectory modeling can identify latent clusters of individuals following similar trajectories across multiple indicators of an outcome. This study sought to: (1) identify trajectories of PCS after mTBI in children, and (2) examine their association with parental and family functioning. Participants were 506 children and adolescents aged 8- to 16-years-old who were recruited during emergency department (ED) visits within 48 h of injury at five Pediatric Emergency Research Canada hospitals. Injury information was collected in the ED, and parental and family functioning was measured at approximately 7 days postinjury. Child and parent PCS ratings were obtained weekly to 3 months and biweekly to 6 months postinjury using the Health and Behavior Inventory. Parental and family functioning were assessed using validated measures of family functioning, parental adjustment, perceived social support from parents, and parental responses to children's symptom complaints. Group-based multitrajectory modeling was used to classify individual children into distinct trajectories of child- and parent-reported cognitive and somatic PCS over time and to examine predictors of those trajectories. Six distinct trajectories were identified: "low acute/resolved PCS" (n = 98), "low acute/declining PCS" (n = 64), "moderate acute/elevated cognitive PCS" (n = 106), "moderate acute/declining PCS" (n = 118), "high acute/declining PCS" (n = 88), and "high acute/persisting PCS" (n = 32). Parental adjustment, protectiveness, and social support were independent predictors of trajectory membership after adjusting for demographic and injury characteristics. The identification of different symptom trajectories and specific aspects of parental and family functioning as predictors of these trajectories provides guidance for developing family-based treatments and targeting treatments to children at risk for poor recovery.

Diffusion tensor imaging studies in children suggest a link between abnormal white matter in limbic-prefrontal circuitry and behavioral problems. However, in children with traumatic injury, links between atypical limbic-prefrontal circuitry and new behavioral problems remain largely unexamined. In a prospective longitudinal study of children ages 8-15 years, we examined white matter microstructure 7 weeks following a traumatic brain injury (TBI) or extracranial injury (EI) relative to typically developing children (TDC). Internalizing and externalizing behavioral problems were assessed via the Child Behavior Checklist; ratings estimated preinjury and 7-month postinjury status. Limbic-prefrontal white matter fiber tracts were estimated using seed-to-seed analysis originating in each amygdala and hippocampus; fractional anisotropy (FA) was calculated along with the tracts. Controlling for preinjury behavior problems, general linear models examined the effect of injury type on behavioral outcomes and pathway FA, including group (TBI+EI vs. TDC; TBI vs. EI), age, sex, and their interactions. Injured children had higher postinjury internalizing problem scores than TDC, and FA was lower in several pathways connecting hippocampi with nucleus accumbens and parahippocampal cingulate. Internalizing and/or externalizing problems were associated with FA of pathways connecting hippocampi to amygdalae, medial orbitalfrontal cortex, and parahippocampal cingulate, as well as pathways connecting amygdale to thalami. The relation between FA and behavioral problems was negative for the TBI group but neutral to positive for the EI and TDC groups. Together, these findings suggest disrupted microstructural organization of the limbic-prefrontal circuitry as a neurobiological predictor of behavioral problems following TBI.

Federal agencies including the National Institutes of Health (NIH), the Department of Defense (DoD) Congressionally Directed Medical Research Program (CDMRP) Spinal Cord Injury Research Program (SCIRP), and the Department of Veterans Affairs (VA) provide the majority of funding for spinal cord injury (SCI) research in the United States. However, systematic evaluation of how funding is distributed across research areas, therapeutic approaches, and translational stages has been limited. To understand the distribution of funds, we curated and classified 1,589 federally funded SCI research awards from the NIH (2008-2023), the CDMRP SCIRP (2009-2023), and the VA (2017-2025). Each award was annotated based on the biological system or problem studied, the therapeutic intervention or approach utilized, and its placement along the translational continuum. Our analysis revealed that the NIH predominantly supports basic and early-stage translational research, especially in areas of SCI pathology, regeneration, and motor functional recovery. In contrast, the CDMRP funding is more concentrated on applied and clinical research, particularly in the areas of pain, bladder function, and neuromodulatory device development. The VA predominantly invests in rehabilitation-focused studies and interventions aimed at improving musculoskeletal and functional health outcomes. While the complementary missions of these agencies collectively support a diverse SCI research ecosystem, we identified critical gaps in funding for high-priority areas such as bowel/gastrointestinal health, cardiovascular function, and mental health. Furthermore, the recent discontinuation of the CDMRP SCIRP and proposed NIH budget reductions are projected to lead to an approximate 50% decline in federal SCI research funding by 2026-posing a substantial risk to the field's progress and threatening the stability of this ecosystem. These findings underscore the urgent need for coordinated, data-driven funding strategies that align more closely with the needs and priorities of the SCI community. To that end, we propose the development of a publicly accessible "living dashboard" to enhance transparency, foster interdisciplinary collaboration, and guide strategic investment in SCI research moving forward.

The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.

In this series of eight articles, the Australian Traumatic Brain Injury Initiative (AUS-TBI) consortium describes the Australian approach used to select the common data elements collected acutely that have been shown to predict outcome following moderate-severe traumatic brain injury (TBI) across the lifespan. This article presents the unified single data dictionary, together with additional measures chosen to facilitate comparative effectiveness research and data linkage. Consultations with the AUS-TBI Lived Experience Expert Group provided insights on the merits and considerations regarding data elements for some of the study areas, as well as more general principles to guide the collection of data and the selection of meaningful measures. These are presented as a series of guiding principles and themes. The AUS-TBI Aboriginal and Torres Strait Islander Advisory Group identified a number of key points and considerations for the project approach specific to Aboriginal and Torres Strait Islander peoples, including key issues of data sovereignty and community involvement. These are outlined in the form of principles to guide selection of appropriate methodologies, data management, and governance. Implementation of the AUS-TBI approach aims to maximize ongoing data collection and linkage, to facilitate personalization of care and improved outcomes for people who experience moderate-severe TBI.

Adverse childhood experiences (ACEs) and traumatic brain injuries (TBI) are highly prevalent globally, and both are associated with long-term negative health outcomes across the lifespan. Past research exploring the potential association between ACEs and TBI occurrence has demonstrated mixed findings. Thus, we conducted a systematic review and meta-analysis to examine the association between the ACEs measure and TBI occurrence. Moderator analyses were conducted to determine whether certain factors, including participant age, sex, and geographical location, modified the association between ACEs score and TBI occurrence. Searches were conducted in PsycINFO, MEDLINE, Embase, and CINHAL for studies published between January 1, 1998, and February 19, 2024. A total of 42 full-text articles were screened against inclusion criteria (i.e., measure of ACEs using the original 8- or 10-item scale or another composite measure of ACEs, TBI occurrence, and effect size for the association between ACEs score and TBI). Eight studies and 10 samples (N = 4954) were included in the meta-analysis. The data were synthesized using a random-effects multilevel meta-analysis, which revealed a significant large positive association between ACEs score and TBI occurrence, r = 0.31, 95% confidence interval [0.13, 0.49], p < 0.001. Moderator analyses did not yield significant results. The current findings demonstrate that individuals who reported a higher ACEs score were more likely to have reported sustaining a TBI, highlighting a need for trauma-informed efforts to prevent TBI and its adverse effects.

Individuals who experience intimate partner violence (IPV) sometimes self-report balance and vestibular problems; however, objectively measured balance has rarely been investigated in this population. Given the risk for persistent physical, neurocognitive, and psychological effects of brain injury (BI) in women who experience IPV, the present study evaluated the association between mild IPV-BIs, objective balance, and self-reported vestibular symptoms in women with at least one instance of physical IPV (n = 144). IPV-BIs and accident-related BIs were assessed using the Ohio State University traumatic BI (TBI) identification method and the Brain Injury Severity Assessment Interview. Psychological symptoms were measured with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Posttraumatic Stress Disorder Checklist for DSM-5. Vestibular symptoms were measured with the Neurobehavioral Symptom Inventory (NSI). Static balance and postural sway were measured with the Sway Medical System Balance Test, for which lower scores reflect worse balance. Hierarchical regression analyses revealed that having a greater number of mild IPV-related BIs was related to (1) lower objectively measured balance scores (adjusting for age, accident-related BIs, and moderate-severe IPV-BIs) and (2) worse self-reported vestibular symptoms on the NSI (adjusting for age, accident-BIs, moderate-severe IPV-BIs, and symptoms of depression, anxiety, and traumatic stress). Worse self-reported vestibular symptoms were also related to lower balance scores. Results from the present study add to the literature describing the complex health problems experienced by women who experience IPV and IPV-related brain injuries. Future research could include in-person evaluations designed to identify treatable vestibular symptoms and problems.