TBI Outcomes Research Articles

Cellular therapy for traumatic brain injury in adults: a meta-analysis of controlled clinical trials

IntroductionTraumatic brain injury (TBI) has got no effective treatment. Cellular therapy is the transfer of autologous or allogeneic cells or cellular material into patient(s) for treatment, showed better outcomes in TBI in several clinical and preclinical studies. We performed a meta-analysis on published articles on the topic of cellular therapy for the treatment of TBI in adult patients.Material and MethodsThe literature search was done via selected database with no restrictions on publication year. Studies were included based on selection criteria and quality assessment. The following data were extracted from included articles; author names, publication year and place, type of study, number, sex and age of participants, type of cells used, and post-treatment follow up. The required data related to Fugl-Meyer Motor Scale (FMMS), Disability Rating Scale (DRS) and patients. Overall improvement was pooled and analyzed using RevMan (Ver.5.4.1).ResultsFive studies that met the selection criteria and considered as high quality, containing 367 participants, with an average follow up time of (7.58±6.93) months, were included in meta-analysis. The results showed that cellular therapy significantly improves (OR=0.26; 95% CI=0.15 to 0.48; P=0.0001) the overall performance of the patients. Moreover, the improvements in FMMS (MD=3.79; 95% CI= -2.53 to 10.10; P=0.24) and DRS (MD= -0.16; 95% CI= -1.51 to 1.19; P=0.82) were not statically significant, but they are obviously clinically significant.ConclusionsThis meta-analysis suggests that cellular therapy improves the condition of TBI patients in clinic. Larger, multi-central trials are required to further confirm and detail the use of stem cells in TBI.

Analysis of moderate and severe traumatic brain injury associated with skull base fracture: a local tertiary center experience

BackgroundTraumatic brain injury (TBI) is a major medical and social concern in developing countries. TBI-related morbidity and mortality statistics in Egypt are lacking and do not reflect the actual magnitude of the problem.ObjectivesTo overview the incidence of moderate and severe head trauma in a heavily populated developing country and document the outcome of moderate and severe TBI associated with skull base fracture (SBF).MethodologyData of patients admitted to our center with moderate and severe TBI associated with skull base fracture (SBF) were reviewed in the period between January 2019 and March 2023.ResultsThe most common type of trauma was road traffic accidents in 54.2% of the patients; 91.2% had Single SBF (middle cranial fossa fracture was predominant 58.5%). 25.5% had an initial GCS of ≤ 8. Periorbital ecchymosis was the most common presenting sign in 36.3%. The most frequent complication (37.3%) was pneumocephalus. The presence of skull base fracture inversely affected the Glasgow outcome scale extended GOSE (P = 0.001, r = 0.674). Higher initial GCS scores were positively correlated with good GOSE (GOSE) (P = 0.001, r =− 0.222).ConclusionsRTA represents a significant cause for moderate and severe TBI in young male population. SBF is associated with poor outcome in moderate and severe TBI. Higher initial GCS score was positively correlated with good GOSE. It is important to have an overview of different types of TBI in Egypt.

Understanding how traumatic brain injury-related changes in fluid biomarkers affect quality of life outcomes in veterans: a prospective observational trial protocol (UNTANGLE)

IntroductionTraumatic brain injury (TBI) is a major cause of disability, with annual global incidence estimated as 69 million people. Survivors can experience long-term visual changes, altered mental state, neurological deficits...

Characteristics of Post-traumatic Shunt-dependent Hydrocephalus After Decompressive Craniectomy: Are Computed Tomography Scoring Systems Predictors?

ObjectiveTraumatic brain injury (TBI) significantly contributes to morbidity rates. While computed tomography (CT) scoring systems have been recognized as predictive factors for TBI outcomes, their association with shunt dependency in patients undergoing decompressive craniectomy (DC) has not been investigated. This study aimed to evaluate the predictive utility of CT scoring systems concerning shunt-dependent hydrocephalus in patients post-DC for TBI. MethodsIn this retrospective study, we enrolled 162 patients who underwent DC and survived more than 7 days following TBI. The pre-DC CT scans were evaluated using the Marshall, Rotterdam, and Helsinki CT scoring systems. The primary event of interest was shunt-dependent hydrocephalus during the follow-up period, with unfavorable outcomes denoted by a Glasgow Outcome Scale score ranging from 1 to 3. ResultsAnalysis of the CT scans showed that the Rotterdam scores had a mean of 4.81 ± 0.91 for the group with shunt-dependent hydrocephalus and 4.41 ± 1.24 for the non-shunt-dependent hydrocephalus group (p = 0.033). However, multivariate logistic regression revealed no significant correlation between the Rotterdam CT score and shunt-dependent hydrocephalus, showing an odds ratio of 1.09 and a 95% confidence interval of 0.71 to 1.67 (p = 0.684). Notably, the Kaplan-Meier outcome curves highlighted a pronounced difference between groups based on shunt dependency (log-rank test: p = 0.012). ConclusionsThe CT scoring systems proved insufficient for predicting shunt-dependent hydrocephalus following DC for TBI. However, our observations underscore a significant correlation between post-traumatic shunt dependency after DC and an increased incidence of unfavorable outcomes during long-term follow-up.

Traumatic brain injury and long-term associations with work, divorce and academic achievement

ObjectiveTraumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement. MethodsUsing a Danish nationwide sample of persons with and without TBI, we employed case-control and longitudinal cohort designs. The case-control design utilized individuals aged 18 to 60 years and examined work stability. Each case, employed at time of TBI, was compared with 10 matched controls. The cohort design utilized individuals alive from 1980 to 2016 with and without TBI and assessed the likelihood of 1) divorce and 2) higher-level education. TBI exposures included concussion, skull fractures, or confirmed TBI. ResultsTBI cases exhibited higher odds ratios (OR) for work instability at all follow-ups compared to controls. Increased TBI severity was associated with a higher risk of work instability at 2-year follow-up (concussion: OR = 1.83; skull fracture: OR = 2.22; confirmed TBI: OR = 4.55), and with a higher risk of not working at 10-year follow-up (confirmed TBI: OR = 2.82; concussion: OR = 1.63). The divorce incidence rate ratio (IRR) was elevated in individuals with TBI (males: IRR = 1.52; females: IRR = 1.48) compared to those without TBI. Individuals with childhood TBI had reduced chances of attaining high school degree or higher (males: IRR = 0.79; females: IRR = 0.85) compared to those without TBI. ConclusionTBI is associated with an increased long-term risk of social consequences, including work instability, divorce, and diminished chances of higher education, even in cases with concussion.

AntiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury.

Aged brains after TBI comprise two pools of CD8 + T cells . The aged brain has long been resided by a population of CD8 + T cells that's exhaustive and dysfunctional. Post TBI, due to BBB impairment, functional CD8 + T cells primarily migrate into the brain parenchyma. Aged, injury-associated microglia with upregulated MHC class I molecules can present neoantigens such as neuronal and/or myelin debris in the injured brains to functional CD8+ T, resulting in downstream CD8+ T cell cytotoxicity. aCD49d Ab treatment exerts its function by blocking the migration of functional effector CD8 + T cell population, leading to less cytotoxicity and resulting in improved TBI outcomes in aged mice.

Traumatic Cerebral Venous Sinus Thrombosis: Management and Outcomes

BackgroundTraumatic brain injury (TBI) with skull fractures parallel to or crossing venous sinuses is a recognized risk factor for traumatic cerebral venous sinus thrombosis (tCVST). Despite the recognition of this traumatic pathology in the literature, no consensus regarding management has been achieved. This study aimed to evaluate the impact of tCVST on TBI outcomes and related complications. MethodPatients within a prospective registry at a Level I trauma center from 2014 to 2023 were reviewed to identify tCVST cases. The impact of tCVST presence on Glasgow Outcome Scale (GOS) scores at 6-months, 30-day mortality, and hospital length of stay were evaluated in multivariable-adjusted analyses. ResultsAmong 607 patients with TBI, 61 patients were identified with skull fractures extending to the vicinity of venous sinuses with dedicated venography. Twenty-eight of these 61 patients (44.3%) had tCVST. The majority (96.4%) of tCVST were located in the unilateral transverse or sigmoid sinus. Complete recanalization was observed in 28% of patients on follow-up imaging (7/25 with follow-up imaging). None of the 28 patients suffered attributable venous infarcts or thrombus propagation. In the adjusted analysis, there was no difference in the 30-day mortality or GOS at 6-months between patients with and without tCVST. ConclusionUnilateral traumatic cerebral venous sinus thrombosis follows a benign clinical course without associated increased mortality or morbidity. The management of traumatic CVST should be distinct as compared to spontaneous CVST, likely without need for anticoagulation.

Inpatient rehabilitation, blood glucose, and the outcome of TBI

Inpatient rehabilitation, blood glucose, and the outcome of TBI

Variability in Standardized Mortality Rates Among Pediatric Traumatic Brain Injury Patients: A Comparative Analysis of Trauma Centers

IntroductionTraumatic brain injury (TBI) causes significant morbidity and mortality in pediatric patients and care is highly variable. Standardized mortality ratio (SMR) summarizes the mortality rate of a specific center relative to the expected rates across all centers, adjusted for case-mix. This study aimed to evaluate variations in SMRs among pediatric trauma centers for TBI. MethodsPatients aged 1–18 diagnosed with TBI within the National Trauma Data Bank (NTDB) from 2017 to 2019 were included. Center-specific SMRs and 95% confidence intervals identified centers with mortality rates significantly better or worse than the median SMR for all centers. Results316 centers with 10,598 patients were included. SMRs were risk-adjusted for patient risk factors. Unadjusted mortality ranged from 16.5 to 29.5%. Three centers (1.5%) had significantly better SMR (SMR <1) and three centers (1.5%) had significantly worse SMR (SMR >1). Significantly better centers had a lower proportion of neurosurgical intervention (2.4% vs. 11.8%, p < 0.001), a higher proportion of supplemental oxygen administration (93.7% vs. 83.5%, p = 0.004) and venous thromboembolism prophylaxis (53.2% vs. 40.6%, p < 0.001) compared to significantly worse centers. ConclusionsThis study identified centers that have significantly higher and lower mortality rates for pediatric TBI patients relative to the overall median rate. These data provide a benchmark for pediatric TBI outcomes and institutional quality improvement. Level of EvidenceLevel III. Type of StudyRetrospective Comparative Study

Surgery, Anesthesia, and TBI Outcomes—Unraveling the Complex Interplay

Surgery, Anesthesia, and TBI Outcomes—Unraveling the Complex Interplay

12‐month cognitive outcome after acute geriatric TBI not associated with U.S. Military Veteran status

AbstractBackgroundTraumatic brain injury (TBI) increases risk for cognitive decline and Alzheimer’s disease/related dementias (ADRD), and Veterans may be at increased risk of both TBI and cognitive decline due to combat/training related exposures and other risk factors. However, it is unknown whether older Veterans are more likely to experience a poor cognitive outcome after acute TBI compared to civilians.MethodWe examined 112 male Veterans and 320 male civilians (55+) who experienced an acute TBI and enrolled in Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK‐TBI). Data were collected at baseline (i.e., emergency room visit) on demographic and injury characteristics. Cognitive and TBI recovery data (i.e., Rivermead Postconcussive Questionnaire, Brief Symptom Inventory, Satisfaction with Life Scale, and Glascow Outcome Scale‐Extended) were collected at 2 weeks, 6 months, and 12 months. We calculated descriptive statistics and compared across Veterans and civilians. 12‐month cognitive outcome was defined as performance &lt;9th percentile on 2+ cognitive tests, and/or decline from 2‐week or 6‐month score &gt;90% reliable change index on two+ tests. We used propensity weighting to address missing cognitive outcome data and conducted a logistic regression analysis to examine association of Veteran status with classification of cognitive outcome.ResultVeterans were older and less likely to be Hispanic compared to civilians but did not differ on race, education, history of head injury, or injury severity. At 12 months post‐TBI, Veterans endorsed worse mood and satisfaction with life (p’s = 0.05), but these results were attenuated by adjustment for prior TBI and injury severity. In adjusted models Veterans did not differ from civilians on a measure of overall TBI outcome (p = 0.45) or postconcussive symptoms (p = 0.32). Moreover, there was no association between Veteran status and cognitive outcome (Wald chi square = 2.66, p = 0.45).ConclusionRisk of poor cognitive outcome following TBI does not differ between older male Veterans and civilians, and mood and life satisfaction outcomes were worse for Veterans but impacted by injury severity and prior head injury. These findings have implications for understanding risk for cognitive decline and ADRD among older men who experience an acute TBI as well as tailoring care, including provision of psychosocial support, for these patients.

Traumatic Brain Injury and Cognitive Aging Among Older Veteran Men – A Twin Study Accounting for Genetics and Medical Conditions

AbstractBackgroundTraumatic brain injury (TBI) is associated with increased risk of dementia, but whether TBI influences cognitive trajectories in later life is less clear. Identifying those at high‐risk of cognitive decline creates intervention opportunities to delay dementia. Since twins share many genes and environmental factors, we capitalize on the twin‐study design to investigate the association between lifetime TBI and cognitive decline.MethodParticipants (n = 8,662) members of the National Academy of Sciences‐National Research Council’s Twins Registry of World‐War‐II Male Veterans born between 1917‐1927 with self or proxy‐reported history of TBI and from one to four assessments over 12 years using the modified‐Telephone Interview for Cognitive Status (TICS‐m). We used linear random‐effects‐mixed models to examine the association between TBI and TICS‐m in the full sample and among co‐twins discordant for TBI. Additional TBI predictor variables included: number and severity (with/without loss‐of‐consciousness[LOC]) of TBI; and age of first TBI (age &lt;25 vs 25+). Models were adjusted for age (centered‐at‐70‐years), age‐squared, education, wave, twin pairs and for lifestyle behaviors and medical conditions. In a subset, we assessed the impact of APOE on TICS‐m.ResultHistory of any TBI, TBI with LOC, and older age of TBI were associated with lower TICS‐m scores at 70‐years (p‐values&lt;0.001). TBI with LOC, more than one TBI, and older age of TBI were associated with faster cognitive decline (p‐values&lt;0.05). Among monozygotic twin pairs discordant for TBI (589 pairs), a history of TBI and having TBI at older age was associated with lower TICS‐m scores (p‐values&lt;0.01); those with more than one TBI and TBI at older age showed greater cognitive decline (p‐values&lt;0.05) compared to their cotwin without TBI. Across all twins, APOE‐e4 carriers with TBI, more than one TBI, TBI with LOC, and older age of TBI had lower TICS‐m scores and greater cognitive decline compared to APOE‐e4 non‐carriers.ConclusionThese findings support an association between TBI and lower cognitive score and more rapid cognitive decline in later life. The results in the monozygotic pairs, who share all genes and many exposures particularly in early life, provide evidence of a causal relationship between TBI and poorer late life cognitive outcomes.

25 Associations between Diffusion Kurtosis Imaging, Tau, and Cognitive Outcomes in TBI

Objective:Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.Participants and Methods:41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.Results:In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).Conclusions:Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

Evaluation of beta-blocker effects on patients with traumatic brain injury: interventional double-blinded randomized controlled trial

BackgroundTraumatic brain injury (TBI) is a major cause of death and disability throughout the world. Traumatic injury is one of the most common causes of death in people under the age of 40 worldwide, and one-third of all trauma-related deaths are a result of intracranial insults. We aimed to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients.ResultRegarding CT brain, 45% of cases in the beta-blocker group and 60% of cases in the control group had abnormal CT findings. Contusion and brain edema were still observed in the beta-blocker group (5% in each), while hemorrhage was still found in 35% of cases in the beta-blocker group and 55% of cases in the control group. Furthermore, a fractured skull was observed in 5% of cases in the beta-blocker group and 20% of cases in the control group. No significant differences were found between the two groups regarding CT brain findings (p-value was > 0.05).Mortality was 15% in the beta-blocker group and 30% in the control group, while 95% of patients in the beta-blocker group and 90% of patients in the control group had ICU stay ≤ 14 days.ConclusionsTotal hospital stay > 14 days showed a significant rise in the beta control group when compared to the blocker group while no significant differences between them in survival, ICU stay, total hospital stay, and total hospital length of stay for patients stayed ≤ 14. Patients in the beta-blocker group showed no significant differences in overall survival compared to patients in the control group.Trial registrationClinicalTrials.gov ID: NCT05195996.

Systemic immune response in young and elderly patients after traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. In addition to primary brain damage, systemic immune alterations occur, with evidence for dysregulated immune responses in aggravating TBI outcome and complications. However, immune dysfunction following TBI has been only partially understood, especially in the elderly who represent a substantial proportion of TBI patients and worst outcome. Therefore, we aimed to conduct an in-depth immunological characterization of TBI patients, by evaluating both adaptive (T and B lymphocytes) and innate (NK and monocytes) immune cells of peripheral blood mononuclear cells (PBMC) collected acutely (< 48 h) after TBI in young (18–45 yo) and elderly (> 65 yo) patients, compared to age-matched controls, and also the levels of inflammatory biomarkers.ResultsOur data show that young respond differently than elderly to TBI, highlighting the immune unfavourable status of elderly compared to young patients. While in young only CD4 T lymphocytes are activated by TBI, in elderly both CD4 and CD8 T cells are affected, and are induced to differentiate into subtypes with low cytotoxic activity, such as central memory CD4 T cells and memory precursor effector CD8 T cells. Moreover, TBI enhances the frequency of subsets that have not been previously investigated in TBI, namely the double negative CD27- IgD- and CD38-CD24- B lymphocytes, and CD56dim CD16- NK cells, both in young and elderly patients. TBI reduces the production of pro-inflammatory cytokines TNF-α and IL-6, and the expression of HLA-DM, HLA-DR, CD86/B7-2 in monocytes, suggesting a compromised ability to drive a pro-inflammatory response and to efficiently act as antigen presenting cells.ConclusionsWe described the acute immunological response induced by TBI and its relation with injury severity, which could contribute to pathologic evolution and possibly outcome. The focus on age-related immunological differences could help design specific therapeutic interventions based on patients’ characteristics.

Does Lower Extremity Fracture Fixation Technique Influence Neurologic Outcomes in Patients with Traumatic Brain Injury? The EAST Brain vs. Bone Multicenter Trial.

To determine whether lower extremity (LE) fracture fixation technique & timing (≤ 24 vs > 24 hours) impact neurologic outcomes in TBI patients. A prospective observational study was conducted across 30 trauma centers. Inclusion criteria were age ≥ 18, head abbreviated injury scale (AIS) score > 2, and a diaphyseal femur or tibia fracture requiring external fixation (Ex-Fix), intramedullary nailing (IMN) or open reduction and internal fixation (ORIF). The analysis was conducted using ANOVA, Kruskal-Wallis, and multivariable regression models. Neurologic outcomes were measured by discharge Ranchos Los Amigos Revised Score (RLAS-R). Of the 520 patients enrolled, 358 underwent Ex-Fix, IMN or ORIF as definitive management. Head AIS was similar among cohorts. The Ex-Fix group experienced more severe LE injuries (AIS 4-5) compared to the IMN group (16% vs 3%, p = 0.01) but not the ORIF group (16% vs. 6%, p = 0.1). Time to operative intervention varied between the cohorts with the longest time to intervention for the IMN group (median hours: Ex-Fix 15 [8-24] vs. ORIF 26 [12-85] vs. IMN 31[12-70], p < 0.001). The discharge RLAS-R score distribution was similar across the groups. After adjusting for confounders, neither method nor timing of LE fixation influenced the discharge RLAS-R. Instead, increasing age and head AIS score were associated with a lower discharge RLAS-R score (OR 1.02, 95% CI 1.002-1.03 and OR 2.37, 95% CI 1.75-3.22) and a higher GCS motor score on admission (OR 0.84, 95% CI 0.73,0.97) was associated with higher RLAS-R score at discharge. Neurologic outcomes in TBI are impacted by severity of the head injury and not the fracture fixation technique or timing. Therefore, the strategy of definitive fixation of LE fractures should be dictated by patient physiology and the anatomy of the injured extremity and not by the concern for worsening neurologic outcomes in TBI patients. Level III (Prognostic/Epidemiological).

Validation of Military Occupational Specialty as a Proxy for Blast Exposure Using the Salisbury Blast Interview.

Evaluations of large datasets preclude the ability to directly measure individual experiences, instead relying on proxies to infer certain constructs. Blast exposure is a construct of study currently in its infancy, resulting in diverse definitions and measurement across studies. The purpose of the present study was to validate Military Occupational Specialty (MOS) as a proxy for blast exposure in combat veterans. 256 veterans (86.33% male) completed the Salisbury Blast Interview (SBI) and Mid-Atlantic MIRECC Assessment of Traumatic Brain Injury (MMA-TBI). MOS was collected through record review and categorized into low and high risk for blast exposure. Chi-square analyses and t-tests compared SBI metrics between MOS categories. ROC analyses evaluated diagnostic accuracy of MOS category in determining blast exposure severity. Veterans in high-risk MOS were more likely to have experienced blast and deployment TBI (p's<.001) compared to low-risk MOS. ROC analyses indicated good specificity (81.29-88.00) for blast and TBI outcomes, suggesting that low-risk MOS is generally associated with an absence of blast and TBI outcomes. Sensitivity was low (36.46-51.14), indicating that MOS risk level was not a good predictor of the presence of these outcomes. Results demonstrate that high-risk MOSs will identify individuals with blast exposure and TBI history whereas low-risk MOSs will capture a highly variable group. Accuracy of MOS categorization was not acceptable for diagnostic-level tests; however, results support its use as a screening measure for a history of exposure to blast, use in epidemiological studies, and considerations for military policy.

Causal discovery replicates symptomatic and functional interrelations of posttraumatic stress across five patient populations.

Approximately half of individuals with posttraumatic stress disorder (PTSD) may meet criteria for other psychiatric disorders, and PTSD symptoms are associated with diminished health and psychosocial functioning. However, few studies examine the longitudinal progression of PTSD symptoms concurrent with related symptom domains and functional outcomes, such that may neglect important longitudinal patterns of symptom progression beyond PTSD specifically. Therefore, we used longitudinal causal discovery analysis to examine the longitudinal interrelations among PTSD symptoms, depressive symptoms, substance abuse, and various other domains of functioning in five longitudinal cohorts representing veterans (n = 241), civilians seeking treatment for anxiety disorders (n = 79), civilian women seeking treatment for post-traumatic stress and substance abuse (n = 116), active duty military members assessed 0-90 days following TBI (n = 243), and civilians with a history of TBI (n = 43). The analyses revealed consistent, directed associations from PTSD symptoms to depressive symptoms, independent longitudinal trajectories of substance use problems, and cascading indirect relations from PTSD symptoms to social functioning through depression as well as direct relations from PTSD symptoms to TBI outcomes. Our findings suggest PTSD symptoms primarily drive depressive symptoms over time, tend to show independence from substance use symptoms, and may cascade into impairment in other domains. The results have implications for refining conceptualization of PTSD co-morbidity and can inform prognostic and treatment hypotheses about individuals experiencing PTSD symptoms along with co-occurring distress or impairment.

Sex-stratified RNA-seq analysis reveals traumatic brain injury-induced transcriptional changes in the female hippocampus conducive to dementia.

Traumatic brain injury (TBI), resulting from a violent force that causes functional changes in the brain, is the foremost environmental risk factor for developing dementia. While previous studies have identified specific candidate genes that may instigate worse outcomes following TBI when mutated, TBI-induced changes in gene expression conducive to dementia are critically understudied. Additionally, biological sex seemingly influences TBI outcomes, but the discrepancies in post-TBI gene expression leading to progressive neurodegeneration between the sexes have yet to be investigated. We conducted a whole-genome RNA sequencing analysis of post-mortem brain tissue from the parietal neocortex, temporal neocortex, frontal white matter, and hippocampus of 107 donors characterized by the Aging, Dementia, and Traumatic Brain Injury Project. Our analysis was sex-stratified and compared gene expression patterns between TBI donors and controls, a subset of which presented with dementia. We report three candidate gene modules from the female hippocampus whose expression correlated with dementia in female TBI donors. Enrichment analyses revealed that the candidate modules were notably enriched in cardiac processes and the immune-inflammatory response, among other biological processes. In addition, multiple candidate module genes showed a significant positive correlation with hippocampal concentrations of monocyte chemoattractant protein-1 in females with post-TBI dementia, which has been previously described as a potential biomarker for TBI and susceptibility to post-injury dementia. We concurrently examined the expression profiles of these candidate modules in the hippocampus of males with TBI and found no apparent indicator that the identified candidate modules contribute to post-TBI dementia in males. Herein, we present the first sex-stratified RNA sequencing analysis of TBI-induced changes within the transcriptome that may be conducive to dementia. This work contributes to our current understanding of the pathophysiological link between TBI and dementia and emphasizes the growing interest in sex as a biological variable affecting TBI outcomes.

High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

AimsTraumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health. Main methodsTo study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI. Key findingsTwo months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume. SignificanceOur research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well.