The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).

The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were "roundtable" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.

Symptoms Associated With Exercise Intolerance and Resting Heart Rate Following Mild Traumatic Brain Injury.

OBJECTIVES: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery. METHODS: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR. RESULTS: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance (P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance (P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) (P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non-sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013). CONCLUSION: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI.

The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.

The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.

PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology. METHODS AND ANALYSIS: PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient's behalf if they lack capacity. Study findings will be disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT05855252.

The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.

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.

The incidence and characteristics of heading in the 2019 FIFA Women's World Cup™.

INTRODUCTION: To quantify the incidence and characteristics of purposeful heading and other head impacts in professional women's football at the 2019 FIFA Women's World Cup™. METHODS: This cross-sectional cohort study analysed purposeful headers (uncontested and contested) and their characteristics (e.g. playing position, match situation, field location, and distance ball travelled), and other head impact events using video analysis. Total headers and head impact events, and incidence rate (IR) per 1000 match-hours were calculated for countries, positions, and other characteristics, such as location on the pitch. RESULTS: Purposeful headers accounted for 76% of all coded events (uncontested: 71%; contested: 29%), followed by attempted headers (21%), unintentional ball-head impacts (2%), and other head impacts (1%). Headers ranged from 0 to 22 per player, per match with a mean of 4.8 [±1.2]. Of all field positions, centrebacks had the highest heading rates and wingers the lowest. Strikers performed significantly more contested headers than any other position, and significantly less uncontested headers. Most headers occurred in the middle third (48%), from free game play (72%) and from long balls (>20 m) (68%). CONCLUSION: The findings of this study could assist the development of player heading risk profiles, sex-specific heading guidelines, and coaching practices.

A retrospective analysis of concussion and post-concussional syndrome diagnoses in Western Australian emergency departments.

OBJECTIVE(S): To determine the rate of concussion diagnoses per capita recorded in hospital emergency departments in Western Australia (WA) from 2002-2018 for ICD-10-AM concussion diagnoses S06.00-S06.05, and post-concussional syndrome (PCS) (F07.2). DESIGN, SETTING AND ANALYSIS: Retrospective analysis of hospital Emergency Department (ED) presentations and hospital admissions from all WA hospitals for all patients with an ICD-10-AM diagnosis code for concussion and post-concussional syndrome (PCS) over the period 2002-2018. Data pertaining to concussion and PCS presentations were extracted from the WA Department of Health Emergency Department Data Collection (EDDC). Total case numbers were aggregated by year (2002-2018) and regions of WA. MAIN OUTCOME MEASURES: The rates of diagnoses were calculated based on the population in the specific region and expressed as incidence rate per 100,000 person-years. The overall trends of diagnoses across the regions were analysed using negative binomial regression models and expressed as incidence rate ratio (IRR) with the corresponding 95 % CI, whilst adjusting for region. Tests for linearity were also performed. RESULTS: The rate of concussion diagnosis had significantly increased linearly over the years (p for trend: p < 0.001) whilst the rate of PCS diagnosis had significantly declined linearly over the same period (p for trend: p < 0.001). CONCLUSION: There was significant increase in all-cause ICD-10-AM concussion diagnoses in WA emergency departments. To further clarify the incidence and prevalence of all-cause concussion in Australia, investigation must focus on truly reflective S06.0 codes and include data linkage to primary care data. Conversely PCS ED presentations reduced; whether this relates to a change in where presentations occur for management of such a diagnosis, improved early intervention or an alternative explanation warrants further investigation.

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.

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: Single Data Dictionary to Predict Outcome for People With Moderate-Severe Traumatic Brain Injury.

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.

Elemental Mapping in a Preclinical Animal Model Reveals White Matter Copper Elevation in the Acute Phase of Central Nervous System Trauma.

Understanding the chemical events following trauma to the central nervous system could assist in identifying causative mechanisms and potential interventions to protect neural tissue. Here, we apply a partial optic nerve transection model of injury in rats and use synchrotron X-ray fluorescence microscopy (XFM) to perform elemental mapping of metals (K, Ca, Fe, Cu, Zn) and other related elements (P, S, Cl) in white matter tracts. The partial optic nerve injury model and spatial precision of microscopy allow us to obtain previously unattained resolution in mapping elemental changes in response to a primary injury and subsequent secondary effects. We observed significant elevation of Cu levels at multiple time points following the injury, both at the primary injury site and in neural tissue near the injury site vulnerable to secondary damage, as well as significant changes in Cl, K, P, S, and Ca. Our results suggest widespread metal dyshomeostasis in response to central nervous system trauma and that altered Cu homeostasis may be a specific secondary event in response to white matter injury. The findings highlight metal homeostasis as a potential point of intervention in limiting damage following nervous system injury.

Neuroimaging to enhance understanding of cardiovascular autonomic changes associated with mild traumatic brain injury: a scoping review.

BACKGROUND: Cardiovascular changes, such as altered heart rate and blood pressure, have been identified in some individuals following mild traumatic brain injury (mTBI) and may be related to disturbances of the autonomic nervous system and cerebral blood flow. METHODS: We conducted a scoping review according to PRISMA-ScR guidelines across six databases (Medline, CINAHL, Web of Science, PsychInfo, SportDiscus and Google Scholar) to explore literature examining both cardiovascular parameters and neuroimaging modalities following mTBI, with the aim of better understanding the pathophysiological basis of cardiovascular autonomic changes associated with mTBI. RESULTS: Twenty-nine studies were included and two main research approaches emerged from data synthesis. Firstly, more than half the studies used transcranial Doppler ultrasound and found evidence of cerebral blood flow impairments that persisted beyond symptom resolution. Secondly, studies utilizing advanced MRI identified microstructural injury within brain regions responsible for cardiac autonomic function, providing preliminary evidence that cardiovascular autonomic changes are a consequence of injury to these areas. CONCLUSION: Neuroimaging modalities hold considerable potential to aid understanding of the complex relationship between cardiovascular changes and brain pathophysiology associated with mTBI. However, it is difficult to draw definitive conclusions from the available data due to variability in study methodology and terminology.

Cannabinoids in traumatic brain injury and related neuropathologies: preclinical and clinical research on endogenous, plant-derived, and synthetic compounds.

Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury. Increased understanding of the endocannabinoid system in health and disease has accompanied growing evidence for therapeutic benefits of Cannabis sativa. This has driven research of Cannabis' active chemical constituents (phytocannabinoids), alongside endogenous and synthetic counterparts, collectively known as cannabinoids. Also of therapeutic interest are other Cannabis constituents, such as terpenes. Cannabinoids interact with neurons, microglia, and astrocytes, and exert anti-inflammatory and neuroprotective effects which are highly desirable for the management of traumatic brain injury. In this review, we comprehensively appraised the relevant scientific literature, where major and minor phytocannabinoids, terpenes, synthetic cannabinoids, and endogenous cannabinoids were assessed in TBI, or other neurological conditions with pathology and symptomology relevant to TBI, as well as recent studies in preclinical TBI models and clinical TBI populations.

Post-Concussion Symptoms, Cognition and Brain Connectivity in an Australian Undergraduate Population: A Quantitative Electroencephalography Study.

BACKGROUND: An estimated 99 in 100,000 people experience a traumatic brain injury (TBI), with 85% being mild (mTBI) in nature. The Post-Concussion Symptom Scale (PCSS), is a reliable and valid measure of post-mTBI symptoms; however, diagnostic specificity is challenging due to high symptom rates in the general population. Understanding the neurobiological characteristics that distinguish high and low PCSS raters may provide further clarification on this phenomenon. AIM: To explore the neurobiological characteristics of post-concussion symptoms through the association between PCSS scores, brain network connectivity (using quantitative electroencephalography; qEEG) and cognition in undergraduates. HYPOTHESES: high PCSS scorers will have (1) more network dysregulation and (2) more cognitive dysfunction compared to the low PCSS scorers. METHODS: A sample of 40 undergraduates were divided into high and low PCSS scorers. Brain connectivity was measured using qEEG, and cognition was measured via neuropsychological measures of sustained attention, inhibition, immediate attention, working memory, processing speed and inhibition/switching. RESULTS: Contrary to expectations, greater frontoparietal network dysregulation was seen in the low PCSS score group (p = 0.003). No significant difference in cognitive dysfunction was detected between high and low PCSS scorers. Post-hoc analysis in participants who had experienced mTBI revealed greater network dysregulation in those reporting a more recent mTBI. CONCLUSIONS: Measuring post-concussion symptoms alone is not necessarily informative about changes in underlying neural mechanisms. In an exploratory subset analysis, brain network dysregulation appears to be greater in the early post-injury phase compared to later. Further analysis of underlying PCSS constructs and how to measure these in a non-athlete population and clinical samples is warranted.

Secondary Degeneration Impairs Myelin Ultrastructural Development in Adulthood following Adolescent Neurotrauma in the Rat Optic Nerve.

Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.

Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats.

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical 'window-of-opportunity' exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury.

What Happens Next? Traumatic Brain Injury in the Community.

Traumatic brain injury (TBI) continues to substantially impact the lives of millions of people around the world annually. Community-based prevention and support of TBI are particularly challenging and underresearched aspects of TBI management. Ongoing cognitive, emotional, and other effects of TBI are not immediately obvious in community settings such as schools, workplaces, sporting clubs, aged care facilities, and support agencies providing homelessness or domestic violence support. This is compounded by a lack of guidance and support materials designed for nonmedical settings. Connectivity Australia, a not-for-profit organization promoting TBI awareness, research, and support, responded to this need by conducting a national survey and series of roundtables to deepen understanding of TBI awareness, challenges, and support needs across the community. The 48 survey respondents and 22 roundtable participants represented Australian departments of health; correctional services; homelessness and housing; Aboriginal and Torres Strait Islander health; community, school, and professional sports; allied healthcare and rehabilitation providers; insurance; and work health and safety. Three key themes were identified: Accessible, nationally consistent plain-language guidelines ; Building research literacy ; and Knowing your role in TBI identification and management . This commentary briefly describes these themes and their implications based on a publicly available full report detailing the study findings ( www.connectivity.org.au/resources-for-researchers/connectivity-research ).

Development of Traumatic Brain Injury Associated Intracranial Hypertension Prediction Algorithms: A Narrative Review.

Traumatic intracranial hypertension (tIH) is a common and potentially lethal complication of moderate to severe traumatic brain injury (m-sTBI). It often develops with little warning and is managed reactively with the tiered application of intracranial pressure (ICP)-lowering interventions administered in response to an ICP rising above a set threshold. For over 45 years, a variety of research groups have worked toward the development of technology to allow for the preemptive management of tIH in the hope of improving patient outcomes. In 2022, the first operationalizable tIH prediction system became a reality. With such a system, ICP lowering interventions could be administered prior to the rise in ICP, thus protecting the patient from potentially damaging tIH episodes and limiting the overall ICP burden experienced. In this review, we discuss related approaches to ICP forecasting and IH prediction algorithms, which collectively provide the foundation for the successful development of an operational tIH prediction system. We also discuss operationalization and the statistical assessment of tIH algorithms. This review will be of relevance to clinicians and researchers interested in development of this technology as well as those with a general interest in the bedside application of machine learning (ML) technology.