Effects Of Traumatic Brain Injury Research Articles

Experiences of caregivers of patients with traumatic brain injury during hospitalization in western China: A qualitative study

ABSTRACT Family members frequently provide both physical and emotional support to patients. Previous studies have focused primarily on the experiences of patients with traumatic brain injury (TBI) and their caregivers during home care and the transition from hospital care to the community, with less emphasis on their experiences during acute hospital care immediately after TBI. This study aimed to explore the experiences of caregivers of patients with TBI during acute hospitalizations. A qualitative descriptive study using individual semistructured interviews was conducted at the trauma center of a tertiary hospital in western China. A purposive sample of 21 caregivers of patients with TBI were recruited. The interviews were conducted face to face in the inpatient ward from July to September 2023. Conventional content analysis was used to conduct the framework analysis. The experiences of caregivers were identified within three key themes: TBI consequences in patients (physical impairments, psychological distress, and cognitive dysfunctions), challenges of caregivers (physiological/emotional/economic burdens, conflicts, and concerns regarding recovery), and needs of caregivers (health information, medical services, and recovery expectations). This study highlights the experiences of caregivers of patients with TBI during hospital stays in western China. The challenges faced by caregivers and the needs of caregivers are multidimensional. Appropriate support should be provided to alleviate the burden of caregiving.

Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury is Linked to Microstructural Plasticity in Prefrontal White Matter.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

Cardiorespiratory fitness and working memory in persons with traumatic brain injury: a cross-sectional analysis

ABSTRACT Introduction Cognitive impairment is a highly impactful consequence of traumatic brain injury (TBI) and there are limited evidence-based treatment practices to combat these impairments. Evidence from other populations suggest that aerobic exercise training (AET) is beneficial for a variety of cognitive deficits, but the research in persons with TBI to date is equivocal. One potential reason is the heterogeneity of exercise prescriptions and outcome measures. This stems from the fact that studies have not been designed based on previous data supporting a specific AET prescription to target a cognitive domain. The primary purpose of this cross-sectional analysis was to examine the relationship between cardiorespiratory fitness (CRF), as a cross-sectional surrogate of AET, and cognition in persons with TBI to inform future research. Methods Cross-sectional analysis was conducted on baseline data of persons with TBI who completed neuropsychological assessments to evaluate several cognitive domains and a cardiopulmonary exercise test (CPET) to measure CRF. Based on the normal distribution of an outcome, Pearson’s r or Spearman’s ρ was calculated to measure the relationship between CRF and cognition. Results Data were analyzed for all participants who demonstrated valid CPETs (n = 21 of 29). Based on the cycle ergometer-based norms of CRF, males in this sample were in the 69th percentile and females in this sample were in the 56th percentile, with high variability across individuals. Higher CRF, as measured by peak power output (Wpeak), was significantly associated with greater working memory (ρ = 0.465, p = 0.017), even after post-hoc corrections. Conclusions These data suggest average and highly variable CRF in persons with TBI of all severity and support cycle ergometry-based CPET testing in this population. Further, these data provide support for future research applying AET to target working memory and possibly other executive functions in persons with TBI. This research is a small step toward large-scale randomized controlled trials that can directly impact clinical care to treat cognitive symptoms post-TBI.

Fluid biomarkers of chronic traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of long-term disability across the world. Evidence for the usefulness of imaging and fluid biomarkers to predict outcomes and screen for the need to monitor complications in the acute stage is steadily increasing. Still, many people experience symptoms such as fatigue and cognitive and motor dysfunction in the chronic phase of TBI, where objective assessments for brain injury are lacking. Consensus criteria for traumatic encephalopathy syndrome, a clinical syndrome possibly associated with the neurodegenerative disease chronic traumatic encephalopathy, which iscommonly associated with sports concussion, have been defined only recently. However, these criteria do not fit all individuals living with chronic consequences of TBI. The pathophysiology of chronic TBI shares many similarities with other neurodegenerative and neuroinflammatory conditions, such as Alzheimer disease. As with Alzheimer disease, advancements in fluid biomarkers represent one of the most promising paths for unravelling the chain of pathophysiological events to enable discrimination between these conditions and, with time, provide prediction modelling and therapeutic end points. This Review summarizes fluid biomarker findings in the chronic phase of TBI (≥6 months after injury) that demonstrate the involvement of inflammation, glial biology and neurodegeneration in the long-term complications of TBI. We explore how the biomarkers associate with outcome and imaging findings and aim to establish mechanistic differences in biomarker patterns between types of chronic TBI and other neurodegenerative conditions. Finally, current limitations and areas of priority for future fluid biomarker research are highlighted.

Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A's ability to target multiple pain pathways may make it a more promising candidate.

The effect of traumatic brain injury on learning and memory: A synaptic focus.

Deficits in learning and memory are some of the most commonly reported symptoms following a traumatic brain injury (TBI). We will examine whether the neural basis of these deficits stems from alterations to bidirectional synaptic plasticity within the hippocampus. Although the CA1 subregion of the hippocampus has been a focus of TBI research, the dentate gyrus should also be given attention as it exhibits a unique ability for adult neurogenesis, a process highly susceptible to TBI-induced damage. This review examines our current understanding of how TBI results in deficits in synaptic plasticity, as well as how TBI-induced changes in endocannabinoid (eCB) systems may drive these changes. Through the synthesis and amalgamation of existing data, we propose a possible mechanism for eCB-mediated recovery in synaptic plasticity deficits. This hypothesis is based on the plausible roles of CB1 receptors in regulating inhibitory tone, influencing astrocytes and microglia, and modulating glutamate release. Dysregulation of the eCBs may be responsible for deficits in synaptic plasticity and learning following TBI. Taken together, the existing evidence indicates eCBs may contribute to TBI manifestation, pathogenesis, and recovery, but it also suggests there may be a therapeutic role for the eCB system in TBI.

Retrospective Outcome Analysis of Geriatric Traumatic Brain Injury Treated at a Tertiary Care Center in India

Abstract Background Trauma is a major cause of morbidity and mortality in elderly patients and its management is challenging. Outcome assessment in these patients is difficult because of preexisting chronic medical conditions as it may be impossible to isolate the effect of traumatic brain injury. This study aimed to examine the clinical outcomes and epidemiological and clinicoradiological characteristics of geriatric traumatic brain injury patients at a tertiary care center. Methods The clinical records of patients aged ≥60 years with head injuries treated at King George's Medical University between 2016 and 2020 were included in the study. Patients were followed up in the outpatient department or through telephone consultation. The follow-up period was updated using the Glasgow outcome score (GOS) of patients for current neurological status and relevant radiological investigations. Results The mean age of subjects was 66.16 ± 6.55 years. Road traffic accidents were the most frequent cause of brain injuries (448 [68.5%]). In total, 41% of the study patients had severe head injuries (Glasgow coma scale, GCS < 9) at admission. The in-hospital mortality was 25.2%. In total, 60.7% of discharged patients showed favorable outcomes (GOS: 4 or 5). GCS at admission, best motor response, and associated comorbidity (diabetes mellitus) significantly predicted the outcome at 6 months. The majority of the patients (82.6 %) were 60 to 70 years of age. Conclusion Road traffic accidents are the most frequent cause of brain injuries in geriatrics. Most of them were managed medically, and majority were discharged (74.8%). Out of those discharged, 39.3% had unfavorable outcomes.

A Narrative Review of Post-traumatic Neuroinflammation: Relevance to Pediatrics.

This is a narrative review that explores the complex interaction between post-traumatic neuroinflammation and its importance in pediatric traumatic brain injuries (TBIs). For immediate and long-term consequences of TBI, neuroinflammation, manifested by activation of microglia and astrocytes, secretion of pro-inflammatory cytokines, as well as breakdown of the blood-brain barrier, are critical factors. While inflammation is an essential part of the brain's repair systems, excessive or prolonged neuroinflammation can lead to more significant neuronal damage, which, in turn, causes persistent cognitive and behavioral deficits over time. In this regard, the paper synthesizes existing evidence concerning molecular and cellular mechanisms that underlie neuroinflammation in relation to TBIamong children, paying attention to age disparities in inflammatory response and their implications for treatment and recovery. Furthermore, it explores how targeted anti-inflammatory therapies are highly likely to improve outcomes for pediatric patients. The outcomes emphasize that there is a need for a more comprehensive understanding of child neuroinflammatory processes and age-specific therapeutic approaches aimed at lessening the effects' negative impacts after brain injury occurs.

Identifying neural correlates of balance impairment in traumatic brain injury using partial least squares correlation analysis

Objective.Balance impairment is one of the most debilitating consequences of traumatic brain injury (TBI). To study the neurophysiological underpinnings of balance impairment, the brain functional connectivity during perturbation tasks can provide new insights. To better characterize the association between the task-relevant functional connectivity and the degree of balance deficits in TBI, the analysis needs to be performed on the data stratified based on the balance impairment. However, such stratification is not straightforward, and it warrants a data-driven approach.Approach.We conducted a study to assess the balance control using a computerized posturography platform in 17 individuals with TBI and 15 age-matched healthy controls. We stratified the TBI participants into balance-impaired and non-impaired TBI usingk-means clustering of either center of pressure (COP) displacement during a balance perturbation task or Berg Balance Scale score as a functional outcome measure. We analyzed brain functional connectivity using the imaginary part of coherence across different cortical regions in various frequency bands. These connectivity features are then studied using the mean-centered partial least squares correlation analysis, which is a multivariate statistical framework with the advantage of handling more features than the number of samples, thus making it suitable for a small-sample study.Main results.Based on the nonparametric significance testing using permutation and bootstrap procedure, we noticed that the weakened theta-band connectivity strength in the following regions of interest significantly contributed to distinguishing balance impaired from non-impaired population, regardless of the type of stratification:left middle frontal gyrus, right paracentral lobule, precuneus, andbilateral middle occipital gyri. Significance.Identifying neural regions linked to balance impairment enhances our understanding of TBI-related balance dysfunction and could inform new treatment strategies. Future work will explore the impact of balance platform training on sensorimotor and visuomotor connectivity.

Family member reported symptom burden, predictors of caregiver burden and treatment effects in a goal-oriented community-based randomized controlled trial in the chronic phase of traumatic brain injury

BackgroundFamily members are often affected by the long-term consequences of traumatic brain injury, but are rarely involved in rehabilitation programs in the chronic phase. We thus do not know what family members´ main concerns are in the chronic phase, what factors are associated with perceived caregiver burden, and whether family members´ health and functioning improves due to rehabilitation efforts received by the patients. This study explored family-members` functioning, predictors of caregiver burden and effect for family members of a goal-oriented intervention in the chronic phase of traumatic brain injury.MethodsFamily members self-reported data measuring their caregiver burden, depression, general health, loneliness, and their evaluation of patient competency in everyday life, patient awareness levels, main problem areas (target outcomes) for the patient related to the brain injury, and demographic data were collected. Regression models were used to explore predictors of caregiver burden, and mixed models analysis was used to explore treatment effects.ResultsIn total, 73 family members were included, 39 in the intervention group and 34 in the control group. Moderate to high caregiver burden was reported by 40% of family members, and 16% experienced clinical levels of depression. Family member loneliness and their evaluation of the patient`s level of functional competency explained 57% of the variability in caregiver burden. There were no treatment-related changes in caregiver burden, family member depression or general health. At T2 there was however a significant reduction in how family members rated severity of target outcomes that the family members had nominated at baseline (-0.38, 95% CI, -0.75 to -0.02, p = 0.04), but not for the target outcomes the patients had nominated.ConclusionsA significant proportion of family members to patients in the chronic phase of TBI continue to experience challenging caregiver burden and emotional symptoms. Both family member-related and patient factors contribute to caregiver burden. Interventions targeting patient complaints do not automatically alleviate family members´ burden. It is important to address social support for family members early after injury, and there is a need for more interventions specifically targeting family members´ needs.Trial registrationThe trial was registered at ClinicalTrials.gov, NCT03545594 on the 4th of June 2018.

Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury: Stage 2 Registered Report.

Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

Outcomes and Mechanisms Associated With Selective Thalamic Neuronal Loss in Chronic Traumatic Brain Injury

The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes. To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes. In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021. Patients with TBI (>6 months postinjury) were compared with healthy control participants (all aged >18 years). Individuals with neurological disease, benzodiazepine use, or contraindication to magnetic resonance imaging were excluded. Data were retrospectively collated with nonconsecutive recruitment, owing to convenience and scanner or PET ligand availability. Data were analyzed between February 1 and September 30, 2023. Flumazenil voxelwise binding potential relative to nondisplaceable binding potential (BPND). Selective neuronal loss identified with FMZ PET was compared between groups on voxelwise and regional scales, and its association with functional, cognitive, and psychological outcomes was examined using Glasgow Outcome Scale (GOS) scores, measures of sustained executive attention (animal and sustained fluency), and 36-Item Short Form Health Survey (SF-36) scores. Diffusion tensor imaging was used to assess structural connectivity of regions of cortical damage, and its association with thalamic selective neuronal loss. In this study, 24 patients with chronic TBI (mean [SD] age, 39.2 [12.3] years; 18 men [75.0%]) and 33 healthy control participants (mean [SD] age, 47.6 [20.5] years; 23 men [69.7%]) underwent FMZ PET. Patients with TBI had a median time of 29 (range, 7-95) months from injury to scan. They displayed selective neuronal loss in thalamic nuclei, over and above gross volume loss in the left thalamus, and bilateral central, mediodorsal, ventral-lateral dorsal, anterior, and ventral anterior thalamic nuclei, across a wide range of injury severities. Neuronal loss was associated with worse functional outcome using GOS scores (left thalamus, left ventral anterior, and bilateral central, mediodorsal, and anterior nuclei), worse cognitive outcome on measures of sustained executive attention (left thalamus, bilateral central, and right mediodorsal nuclei), and worse emotional outcome using SF-36 scores (right central thalamic nucleus). Chronic thalamic neuronal loss partially mirrored the location of primary cortical contusions, which may indicate secondary injury mechanisms of transneuronal degeneration. The findings of this study suggest that selective thalamic vulnerability may have chronic neuronal consequences with relevance to long-term outcome, suggesting the evolving and potentially lifelong thalamic neuronal consequences of TBI. FMZ PET is a more sensitive marker of the burden of neuronal injury than routine imaging; therefore, it could inform outcome prognostication and may lead to the development of individualized precision medicine approaches.

The Effect of Oleuropein in AIF and MMP-9 in Traumatic Brain Injury Rat Model.

Traumatic brain injury is a significant public problem with an incidence of 10 million people per year, causing the largest deaths and disabilities worldwide. Head injuries can be classified into primary and secondary head injuries. Secondary head injuries can be caused by several factors such as ischemia, cerebral edema, and neuroinflammation. AIF and MMP-9 are two parameters that can be indicators in measuring the effect of Oleuropein on traumatic brain injury in rats. Oleuropein itself has many activities such as antioxidant, anti-apoptotic, antimicrobial, anti-inflammatory, and neuroprotective. Adult male Sprague-Dawley rats (250-350 grams) were exposed to head injury, with or without intraperitoneal administration of Oleuropein. Within 24-72 hours brain tissue was isolated for immunohistochemical analysis, ELISA, and TUNEL. AIF, GFAP, MMP-9, and HMGB-1 levels were determined using immunohistochemistry in both the control and treatment groups. Statistical analysis was made using the One-Way Analysis of Variance (ANOVA) and paired t-test. The results showed that Oleuropein was able to reduce AIF and MMP-9 levels in rats with traumatic brain injury. This indicates that Oleuropein has a neuroprotective effect by reducing inflammation and apoptosis. Oleuropein has a potential neuroprotective effect in traumatic brain injury by reducing inflammation and apoptosis. Therefore, Oleuropein can be considered as a potential therapeutic agent for traumatic brain injury in the future.

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt.

In vivo glutamate sensing has provided valuable insight into the physiology and pathology of the brain. Electrochemical glutamate biosensors, constructed by cross-linking glutamate oxidase onto an electrode and oxidizing H2O2 as a proxy for glutamate, are the gold standard for in vivo glutamate measurements for many applications. While glutamate sensors have been employed ubiquitously for acute measurements, there are almost no reports of long-term, chronic glutamate sensing in vivo, despite demonstrations of glutamate sensors lasting for weeks in vitro. To address this, we utilized a platinum electrode with nanometer-scale roughness (nanoPt) to improve the glutamate sensors' sensitivity and longevity. NanoPt improved the GLU sensitivity by 67.4% and the sensors were stable in vitro for 3 weeks. In vivo, nanoPt glutamate sensors had a measurable signal above a control electrode on the same array for 7 days. We demonstrate the utility of the nanoPt sensors by studying the effect of traumatic brain injury on glutamate in the rat striatum with a flexible electrode array and report measurements of glutamate taken during the injury itself. We also show the flexibility of the nanoPt platform to be applied to other oxidase enzyme-based biosensors by measuring γ-aminobutyric acid in the porcine spinal cord. NanoPt is a simple, effective way to build high sensitivity, robust biosensors harnessing enzymes to detect neurotransmitters in vivo.

The Effect of Traumatic Brain Injury on Memory.

Having a good memory is essential for carrying out daily tasks. People cannot study, plan, remember or navigate life effectively if they are memoryless. People may be at risk when mistakes made in the past will be repeated and lessons regarding danger cannot be learned. In the community, traumatic brain injury (TBI) is common and individuals with TBI frequently have memory problems. It is crucial to study how TBI affects memory to better understand the underlying mechanism and to tailor rehabilitation for patients with a range of pathologies and severity levels. Thus, this paper aimed to review studies related to TBI's effect on memory. This review examined recent studies to learn more regarding and comprehend the connection between TBI and memory, including short-term memory (STM), working memory (WM) and long-term memory (LTM). This will undoubtedly have a big impact on how memory problems that may arise after TBI will be addressed. Virtual reality and other technological advancements have given the medical community a new way to investigate rehabilitative therapy.

Reduced income, joblessness, and disability among traumatic brain injury survivors: A national cohort study in South Korea

ObjectiveThis study aimed to investigate the effects of traumatic brain injury (TBI) on employment status, household income, and the development of new disabilities among survivors, as well as its correlation with mortality rates over a 2-year period. MethodsIn this nationwide population-based cohort study, we screened all patients admitted to the intensive care unit (ICU) because of TBI between January 1, 2010, and December 31, 2018, in South Korea. Among them, patients who were alive for > 1 year were considered TBI survivors. Changes in unemployment, decreased household income, and newly acquired disabilities were evaluated one year after the date of ICU admission due to TBI. ResultsIn total, 78,420 TBI survivors were included in this study. Among them, 5.4 %, 22.5 %, and 8.6 % of the TBI survivors experienced unemployment, decreased household income, and newly acquired disabilities within one year after the date of ICU admission, respectively. A longer ICU stay, comorbidities, hospital admission through the emergency room, increased total cost of hospitalization, and mechanical ventilatory support were associated with unemployment, decreased household income, and newly acquired disabilities. Among the three factors, the newly acquired disability was associated with a 27 % increase in 2-year all-cause mortality (hazard ratio: 1.27, 95 % confidence interval: 1.17–1.39; P < 0.001), while unemployment and decreased household income were not significantly associated (P = 0.371 and P = 0.105, respectively). ConclusionsA significant number of individuals in South Korea who survived TBI faced challenges such as unemployment, reduced household income, and the acquisition of new disabilities within a year of being admitted to the ICU. In addition, the study found that individuals who developed a new disability after TBI had a higher risk of mortality within two years.

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

Epidemiology of Intimate Partner and Domestic Violence-Related Traumatic Brain Injury in the United States, 2018 to 2021: A National Trauma Data Bank Cohort Analysis of 3891 Patients.

Despite profound medico-socio-legal consequences of traumatic brain injury (TBI) from intimate partner violence and domestic violence (IPV/DV), the incidence and acute outcomes of concurrent IPV/DV-TBI are not well understood. We examined US IPV/DV patients with/without TBI (IPV/DV-TBI; non-TBI) using the National Trauma Data Bank. We hypothesized IPV/DV-TBI would be associated with elevated morbidity. National Trauma Data Bank Trauma Quality Programs Participant Use Files years 2018 to 2021 were queried for patients aged ≥18 years with IPV/DV using International Classification of Diseases, Tenth Revision external cause codes. TBI/non-TBI was defined using International Classification of Diseases, Tenth Revision diagnosis codes. TBI severity was defined by the Glasgow Coma Scale (severe = 3-8, moderate = 9-12, and mild = 13-15). Outcomes were intensive care unit (ICU) admission, in-hospital mortality, length of stay (LOS), and discharge home. Multivariable regressions examined associations between TBI and outcomes, controlling for sociodemographic and injury severity variables. Of 3891 IPV/DV-related cases, 31.1% were IPV/DV-TBI. Cranial injuries included skull fracture (30.2%), subdural (19.8%), subarachnoid (13.4%), and epidural (1.1%) hemorrhage, contusion (8.1%), and cerebral edema (3.3%). In IPV/DV-TBI, mild/moderate/severe TBI proportions were 87.4%/4.3%/8.3%, with mean LOS 11.5 ± 10.9/14.4 ± 27.3/5.0 ± 7.7-days and mortality 0.9%/22.5%/28.6%, respectively. Compared with non-TBI, IPV/DV-TBI had more female (77.2%/64.6%, P < .001) and fewer Black patients (28.9%/36.6%, P < .001), more ICU admissions (20.9%/7.5%, P < .001) and mortality (4.1%/1.8%, P < .001), longer LOS (5.3 ± 9.5/4.5 ± 6.4-days, P = .008), and decreased discharge home (79.8%/83.8%, P = .005). Multivariable regressions confirmed the associations between TBI and ICU admission (adjusted odds ratio [aOR] = 4.29, 95% CI [3.46-5.33]), mortality (aOR = 3.20 [1.99-5.15]), LOS (adjusted mean difference = +1.22 [0.68-1.76]), and inability to discharge home (aOR = 0.57 [0.46-0.71]). One-third of US IPV/DV-related trauma cases have TBI, comprising predominantly female patients. Black patients with IPV/DV-related trauma were overrepresented compared with US census estimates. IPV/DV-TBI had increased ICU admissions, LOS, in-hospital mortality, and inability to discharge home compared with non-TBI. Investigating morbidity risk factors and providing sociomedical resources during acute care are critically needed in this vulnerable population.

VX‐765 alleviates motor and cognitive impairments via inhibiting PANoptosis activation in the neonatal rats after hypoxic–ischemic brain damage

AbstractNeonatal hypoxia–ischemia (HI) is one of the main factors that cause neonatal severe neurologic impairment and death. Shown by a large number of studies, caspase‐1 plays a significant effect in diseases such as hypoxic–ischemic brain damage (HIBD) and may be a key component of the protein complex that initiates PANoptosis. VX‐765, an inhibitor of caspase‐1, exerts a potential neuroprotective effect in traumatic brain injury. However, it is unknown whether the administration of VX‐765 has neuroprotective effects on neonatal rats that suffered HIBD, and if so, the underlying mechanisms are also still unknown. In the present study, we found that treatment with VX‐765 (50 mg/kg, i.p.) significantly ameliorated the impairment of locomotor coordination functions and myodynamia as well as the spatial learning and memory in neonatal rats subjected with HIBD. These behavior improvements were attributed to VX‐765 reducing infarct volumes and neuronal loss in the CA1, CA3 region of hippocampus, and deeper layers of the cortex in HIBD rats. Moreover, the enzyme‐linked immunosorbent assay showed that VX‐765 obviously decreased the production of neuroinflammatory factors including TNF‐α, IL‐1β, and IL‐6. Importantly, we identified HI promoted PANoptosis activation in vivo and in vitro, and VX‐765 obviously suppressed PANoptosis activation. Finally, we demonstrated that VX‐765 treatment reversed neuronal injury induced by oxygen–glucose deprivation (OGD). Taken together, these results suggest that VX‐765 protects the neurons against damage by suppressing neuroinflammation and PANoptosis activation, thereby improving locomotor coordination and cognitive impairments in neonatal HIBD rats, indicating that VX‐765 may be an underlying therapeutic drug for the clinical treatment of hypoxic–ischemic encephalopathy (HIE).

Modeling Mild Traumatic Brain Injury In-Vitro Using PHuman Choroid Plexus Endothelial Cells

Over 2.5 million Traumatic Brain Injuries (TBIs) occur each year due to falls, motor vehicle accidents, assaults, and sports (Brain Trauma Foundation, 2023). Short- and long-term consequences of TBI can include headache, cognitive impairment, seizures, hypoxia, and ischemia. Human TBI studies are diffcult due to the confounding variables of type and mechanism of injury, severity of injury, and length of time to present to emergency departments. While animal models exist, it is our goal to develop an in-vitro model of TBI using primary human brain cell cultures to examine cellular responses in real time. While the blood-brain barrier has been studied extensively post-TBI due to its role in ischemia and hypoxia, there is a dearth of research on the blood-CSF-barrier (BCSFB), the choroid plexus, and its response post-TBI. After culturing primary human choroid plexus endothelial cells (ScienCell Cat #1300) on a flexible membrane, we subjected them to mechanical strain using the FlexCell tension system and collected supernatant at 3-, 6-, 12-, 24-, 48-, 72-, and 96-hours post injury. The FlexCell tension bioreactor system uses positive and negative air pressure to apply mechanical elongation strain mimicking mild shearing injury. Using R&amp;D cytokine arrays (R&amp;D Systems, Cat# ARY005B), we measured 36 different cytokines, chemokines and acute phase proteins including C5a, GM-CSF, ICAM-1, IL-1, IL-6, TNFα, IFNγ, CCL5/RANTES, etc. We hypothesized that we would see a pro-inflammatory response (IL-1β, IL-6, TNFα) within 24 hours after one or two 12% mechanical strain injuries compared to the control of no strain, as seen in the literature. However, there were not significant increases in cytokine signaling until 24-48 hours post-injury, and in regulatory cytokines, such as CCL2, MIP1α/MIP1β, IL-2, IL-12, &amp; IL-17, that lasted as long as 96-hours. This effect was more pronounced in the two strain verses one strain model and control, as expected. Interestingly, anti-inflammatory cytokine IL-10 was significantly increased in the one strain model, but not two strain model, 48 hours post-insult. As the choroid plexus is a niche for T cell stimulation in the central nervous system (Strominger et al., 2018), these results indicate a complex immunological response that seems to favor T-Cell response over monocytes/macrophages. These experiments were completed with the lowest mechanical strain of the FlexCell system and future experiments are warranted to determine if a stronger mechanical strain is needed to produce the pro-inflammatory response seen in the literature in mild to severe models of TBI. This project was funded by a Senior Research Grant from the Indiana Academy of Science and from a Faculty Research Development Grant from Marian University College of Osteopathic Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.