Association of Cadherin-Related Family Member 1 with Traumatic Brain Injury.

The cadherin family plays a pivotal role in orchestrating synapse formation in the central nervous system. Cadherin-related family member 1 (CDHR1) is a photoreceptor-specific calmodulin belonging to the expansive cadherin superfamily. However, its role in traumatic brain injury (TBI) remains largely unknown. CDHR1 expression across various brain tissue sites was analyzed using the GSE104687 dataset. Employing a summary-data-based Mendelian Randomization (SMR) approach, integrated analyses were performed by amalgamating genome-wide association study abstracts from TBI with public data on expressed quantitative trait loci and DNA methylation QTL from both blood and diverse brain tissues. CDHR1 expression and localization in different brain tissues were meticulously delineated using western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay. CDHR1 expression was consistently elevated in the TBI group compared to that in the sham group across multiple tissues. The inflammatory response emerged as a crucial biological mechanism, and pro-inflammatory and anti-inflammatory factors were not expressed in either group. Integrated SMR analyses encompassing both blood and brain tissues substantiated the heightened CDHR1 expression profiles, with methylation modifications emerging as potential contributing factors for increased TBI risk. This was corroborated by western blotting and immunohistochemistry, confirming augmented CDHR1 expression following TBI. This multi-omics-based genetic association study highlights the elevated TBI risk associated with CDHR1 expression coupled with putative methylation modifications. These findings provide compelling evidence for future targeted investigations and offer promising avenues for developing interventional therapies for TBI.

Chronic glial activation and behavioral alterations induced by acute/subacute pioglitazone treatment in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is a disabling neurotraumatic condition and the leading cause of injury-related deaths and disability in the United States. Attenuation of neuroinflammation early after TBI is considered an important treatment target; however, while these inflammatory responses can induce secondary brain injury, they are also involved in the repair of the nervous system. Pioglitazone, which activates peroxisome proliferator-activated receptor gamma, has been shown to decrease inflammation acutely after TBI, but the long-term consequences of its use remain unknown. For this reason, the impacts of treatment with pioglitazone during the acute/subacute phase (30 min after injury and each subsequent 24 h for 5 days) after TBI were interrogated during the chronic phase (30- and 274-days post-injury (DPI)) in mice using the controlled cortical impact model of experimental TBI. Acute/subacute pioglitazone treatment after TBI results in long-term deleterious consequences, including disruption of tau homeostasis, chronic glial cell activation, neuronal pathology, and worsened injury severity particularly at 274 DPI, with male mice being more susceptible than female mice. Further, male pioglitazone-treated TBI mice exhibited increased dominant and offensive-like behavior while having a decreased non-social exploring behavior at 274 DPI. After TBI, both sexes exhibited glial activation at 30 DPI when treated with pioglitazone; however, while injury severity was increased in females it was not impacted in male mice. This work reveals that although pioglitazone has been shown to lead to attenuated TBI outcomes acutely, sex-based differences, timing and long-term consequences of treatment with glitazones must be considered and further studied prior to their clinical use for TBI therapy.

Mild and Severe Blood Alcohol Concentration Effects on Trauma and Traumatic Brain Injury Outcomes.

INTRODUCTION: Reported outcomes for trauma patients (TPs) with elevated blood alcohol concentration (BAC) have been mixed. Previous studies suggest that positive BAC might lead to lower venous thromboembolism (VTE) rates and mortality. This study expands upon these findings by examining the association of various levels of BAC, with additional emphasis on traumatic brain injury (TBI) patients. We hypothesize that both mild and severe-BAC levels in TPs are associated with decreased risk of VTE and mortality. METHODS: A retrospective review of the 2017 Trauma Quality Improvement Program was performed on adults (≥18 y old) screened for BAC on admission. Patients deceased on arrival and positive for drugs were excluded. We compared three groups: no-BAC, mild-BAC (0-70 mg/dL), and-severe BAC (>80 mg/dL) for associated risk of VTE and mortality. RESULTS: From 203,535 tested patients, 118,427 (58.2%) had no-BAC, 19,813 (9.7%) had mild-BAC, and 65,295 (32.1%) had severe-BAC. The associated risk of VTE was lower for mild-BAC (odds ratios [OR] 0.69, 0.58-0.82, P < 0.001) and severe-BAC (OR 0.80, 0.72-0.89, P < 0.001). This persisted in TBI patients, with mild-BAC (OR 0.67, 0.51-0.89, P = 0.006) and severe-BAC (OR 0.75, 0.64-0.89, P < 0.001) groups exhibiting lower associated VTE risk. However, the associated mortality risk was lower only in severe-BAC patients (OR 0.90, 0.83-0.97, P = 0.009). CONCLUSIONS: A positive BAC is linked to a reduced associated risk of VTE in TPs, including those with TBI. Notably, only the severe-BAC group demonstrated a lower associated risk of mortality. This merits future research including identification of basic science pathways that may be targeted to improve outcomes.

Letter to the editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis.

The meta-analysis by Shen et al. in Neurosurgical Review highlights the benefits of brain tissue oxygen partial pressure (PbtO2) monitoring in reducing mortality and intracranial pressure in severe traumatic brain injury (TBI) patients. However, it also associates PbtO2 monitoring with prolonged hospital stays. Future research should focus on standardizing PbtO2 protocols, integrating with advanced neuroimaging, exploring long-term outcomes, evaluating combination therapies, and conducting cost-benefit analyses. Addressing these areas could further enhance the clinical application and efficacy of PbtO2 monitoring in improving patient outcomes.

Letter to editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis of published cases.

This critique evaluates a letter to the editor discussing the role of brain tissue oxygen partial pressure (PbtO2) monitoring in the prognosis of patients with traumatic brain injury (TBI). The meta-analysis aims to synthesize existing evidence, highlighting the potential of PbtO2 monitoring as an early indicator of cerebral hypoxia and its correlation with improved patient outcomes. Despite these promising findings, the analysis is constrained by significant methodological variability among the included studies, potential publication bias, and the practical challenges of implementing PbtO2 monitoring widely. The letter emphasizes the need for standardized protocols and further research to solidify the clinical utility of PbtO2 monitoring and integrate it with other monitoring strategies for comprehensive TBI management.

"Biomarkers in severe traumatic brain injury: enhancing prognostic accuracy and therapeutic strategies".

This study examines the emerging role of biomarkers in the prognosis and management of severe traumatic brain injury (sTBI). Key findings highlight the significance of serum RIP-3, STC1, Nrf2, and cerebrospinal fluid galectin-3 and cytokines in predicting disease severity, mortality, and functional outcomes in sTBI patients. Elevated levels of RIP-3 and STC1 were linked to poor prognosis and increased mortality, with RIP-3 associated with necroptosis and inflammation, and STC1 with neuroprotective properties. Nrf2 was found to correlate with oxidative stress and adverse outcomes, while elevated CSF galectin-3 and IL-6 indicated neuroinflammation and neurodegeneration. These biomarkers show promise not only as prognostic tools but also as potential therapeutic targets. The study suggests further validation through multicenter research to enhance clinical applications and improve treatment strategies for sTBI.

Attrition, adherence, and compliance to exercise training interventions in persons with traumatic brain injury: a systematic review of training studies.

BACKGROUND: Exercise training (ET) is a promising rehabilitation approach for long-term negative consequences of traumatic brain injury (TBI). However, little is known regarding overall rates of attrition, adherence, and compliance to ET in TBI. OBJECTIVE: The purpose of this systematic review was to estimate average attrition, adherence, and compliance rates in ET studies in persons with TBI. METHODS: Databases were searched from inception to April 15, 2024. Two authors independently extracted data related to attrition, adherence, compliance, and possible moderators identified a priori. RESULTS: The average rate of attrition from 45 studies was 14.4%, although the majority of studies had small sample sizes (i.e. n < 42). Based on hierarchical linear regression, the most influential predictors of attrition were sample size and study design. A minority of studies reported adherence (44.4%) or compliance (22.2%) but those that did reported good average adherence (85.1%) and compliance (77.7%). These studies support the ability of persons with TBI to complete an ET intervention as prescribed. CONCLUSIONS: Researchers can use this information to ensure adequate power to detect a true effect of ET in persons with TBI. Researchers conducting ET studies in persons with TBI should clearly and thoroughly report data on attrition, adherence, and compliance.

Quantitative Pupillometry for Intracranial Pressure (ICP) Monitoring in Traumatic Brain Injury: A Scoping Review.

The neurological examination has remained key for the detection of worsening in neurocritical care patients, particularly after traumatic brain injury (TBI). New-onset, unreactive anisocoria frequently occurs in such situations, triggering aggressive diagnostic and therapeutic measures to address life-threatening elevations in intracranial pressure (ICP). As such, the field needs objective, unbiased, portable, and reliable methods for quickly assessing such pupillary changes. In this area, quantitative pupillometry (QP) proves promising, leveraging the analysis of different pupillary variables to indirectly estimate ICP. Thus, this scoping review seeks to describe the existing evidence for the use of QP in estimating ICP in adult patients with TBI as compared with invasive methods, which are considered the standard practice. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Eight studies were included for analysis, with the vast majority being prospective studies conducted in high-income countries. Among QP variables, serial rather than isolated measurements of neurologic pupillary index, constriction velocity, and maximal constriction velocity demonstrated the best correlation with invasive ICP measurement values, particularly in predicting refractory intracranial hypertension. Neurologic pupillary index and ICP also showed an inverse relationship when trends were simultaneously compared. As such, QP, when used repetitively, seems to be a promising tool for noninvasive ICP monitoring in patients with TBI, especially when used in conjunction with other clinical and neuromonitoring data.

Using Optic Nerve Sheath Diameter for Intracranial Pressure (ICP) Monitoring in Traumatic Brain Injury: A Scoping Review.

INTRODUCTION: Neuromonitoring represents a cornerstone in the comprehensive management of patients with traumatic brain injury (TBI), allowing for early detection of complications such as increased intracranial pressure (ICP) [1]. This has led to a search for noninvasive modalities that are reliable and deployable at bedside. Among these, ultrasonographic optic nerve sheath diameter (ONSD) measurement is a strong contender, estimating ICP by quantifying the distension of the optic nerve at higher ICP values. Thus, this scoping review seeks to describe the existing evidence for the use of ONSD in estimating ICP in adult TBI patients as compared to gold-standard invasive methods. MATERIALS AND METHODS: This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Sixteen studies were included for analysis, with all studies conducted in high-income countries. RESULTS: All of the studies reviewed measured ONSD using the same probe frequency. In most studies, the marker position for ONSD measurement was initially 3 mm behind the globe, retina, or papilla. A few studies utilized additional parameters such as the ONSD/ETD (eyeball transverse diameter) ratio or ODE (optic disc elevation), which also exhibit high sensitivity and reliability. CONCLUSION: Overall, ONSD exhibits great test accuracy and has a strong, almost linear correlation with invasive methods. Thus, ONSD should be considered one of the most effective noninvasive techniques for ICP estimation in TBI patients.

Who is seeking information about traumatic brain injury? Characterizing online course participants.

Accessible, up-to-date information on traumatic brain injury (TBI) can be challenging to find and is needed to address TBI knowledge gaps and improve outcomes for people who experience a TBI. The Understanding TBI Massive Open Online Course (TBI MOOC) was developed to increase TBI knowledge across a diverse global audience. We sought to characterize the TBI MOOC participant cohort, to understand the reach of the course among this target audience. Examining the characteristics of TBI MOOC enrollees showed that participants came from a wide range of demographic backgrounds, had a variety of TBI experiences and had multiple reasons for enrolling in the MOOC. The majority of course participants shared some characteristics with other groups of health information seekers. Four distinct demographic profiles were identified among TBI MOOC participants (education seekers, TBI-aware participants, TBI care providers and retirees) using a novel approach combining chi-squared tests and network modularity. Participants assigned to the TBI-aware and retiree profiles were most likely to complete all modules of the MOOC, and the TBI-aware profile was more highly represented in more recent iterations of the MOOC. Together, these data indicate that the TBI MOOC provided information to a wide range of people, and particularly engaged participants with personal or family experience of TBI. However, engagement with this course was minimal among some hard-to-reach populations, including men and people with low levels of education, indicating that additional strategies are needed to ensure equity in health promotion.

Stakeholder views on cognitive communication assessment and intervention for a person living independently in the community with severe traumatic brain injury.

BACKGROUND: Cognitive communication disorder (CCD) following traumatic brain injury (TBI) is well documented and these communication problems impede successful re-integration into community living. While there is growing evidence for intervention to both detect and treat the impact of these deficits across the rehabilitation continuum, there are barriers to accessing services. Cognitive communication impairments may be missed because the person can talk, and this may mask the subtle but debilitating impact of a CCD. Referral to a speech and language therapist (SLT) may be overlooked or not timely, which prevents the individual accessing evidence-based interventions. Inadequate treatment provision and an under- or overestimation of communication capability can potentially undermine the effectiveness of wider team assessment and intervention. AIMS: To report stakeholder views on specialist SLT input for CCD within a multidisciplinary team intervention for a community-dwelling individual with severe TBI. The investigation explored perspectives on understanding of CCD, on practice and on outcomes, in order to inform professional groups on perceived impacts of the evidence-to-practice gap. METHODS AND PROCEDURES: A semi-structured interview methodology was employed with 11 stakeholder participants involved in a single case. Data were evaluated using a thematic framework method. Themes were inductively derived from the stakeholder narratives. OUTCOMES: Stakeholders reported the following outcomes from specialist SLT input for CCD within a collaborative team approach: improved engagement with rehabilitation and support teams, improved health-related quality of life and well-being, and increased client participation in community activities of personal relevance. Stakeholders also reported inequities in wider service provision where limitations in professional understanding of CCD and knowledge of best practice recommendations preclude access to specialist SLT services. CONCLUSIONS: CCDs are under-recognised and this can have a devastating effect on people with CCD and on those around them. Stakeholder reports provide evidence for the effectiveness of SLT practice recommendations for the treatment of CCD following TBI. They also provide additional evidence of persisting barriers to accessing treatment. Future research to explore ways to close this evidence-to-practice gap is required. WHAT THIS PAPER ADDS: What is already known on this subject Cognitive communication difficulties are a well-documented consequence of TBI. There is evidence for the effectiveness of person-centred interventions for CCD across the recovery continuum. International evidence-based practice recommendations are in place for CCD assessment and management. Barriers to accessing SLT expertise for CCD have previously been reported. What this paper adds to existing knowledge This investigation explores the views of a diverse group of stakeholders involved in a single case of a community-dwelling individual with severe TBI. Stakeholders report positive real-world outcomes from SLT interventions for CCD within a coordinated multidisciplinary rehabilitation team. Stakeholder reports also indicate inequities in wider service provision and CCD knowledge gaps amongst professional groups providing rehabilitation services for people with TBI. What are the potential or actual clinical implications of this work? CCDs are under-recognised, with devastating effect for people with CCD and those around them. These findings underscore the importance of raising professional awareness of CCD and best practice recommendations, in order to improve access to SLT expertise for people with CCD following TBI.

A Systematic Review of the Relationship Between Traumatic Brain Injury and Disruptions in Heart Rate Variability.

Autonomic nervous system dysfunction is increasingly recognized as a common sequela of traumatic brain injury (TBI). Heart rate variability (HRV) is a specific measure of autonomic nervous system functioning that can be used to measure beat-to-beat changes in heart rate following TBI. The objective of this systematic review was to determine the state of the literature on HRV dysfunction following TBI, assess the level of support for HRV dysfunction following TBI, and determine if HRV dysfunction predicts mortality and the severity and subsequent recovery of TBI symptoms. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two raters coded each article and provided quality ratings with discrepancies resolved by consensus. Eighty-nine papers met the inclusion criteria. Findings indicated that TBI of any severity is associated with decreased (i.e., worse) HRV; the severity of TBI appears to moderate the relationship between HRV and recovery; decreased HRV following TBI predicts mortality beyond age; HRV disturbances may persist beyond return-to-play and symptom resolution following mild TBI. Overall, current literature suggests HRV is decreased following TBI and may be a good indicator of physiological change and predictor of important outcomes including mortality and symptom improvement following TBI.

Unveiling the performance of the prehospital Rapid Emergency Medicine Score (pREMS): How the predictive score impacts in-hospital outcomes in traumatic brain injury (TBI): A retrospective observational cohort study.

INTRODUCTION: This study aimed to evaluate the predictive accuracy of the prehospital rapid emergency medicine score (pREMS) for predicting the outcomes of hospitalized patients with traumatic brain injury (TBI) who died, were discharged, were admitted to the intensive care unit (ICU), or were admitted to the operating room (OR) within 72 h. METHODS: A retrospective cohort analysis was performed on a sample of 513 TBI patients admitted to the emergency department (ED) of Besat Hospital in 2023. Only patients of both sexes aged 18 years or older who were not pregnant and had adequate documentation of vital signs were included in the analysis. Patients who died during transport and patients who were transferred from other hospitals were excluded. The predictive power of the pREMS for each outcome was assessed by calculating the sensitivity and specificity curves and by analyzing the area under the receiver operating characteristic curve (AUROC). RESULTS: The mean pREMS scores for hospital discharge, death, ICU admission and OR admission were 11.97 ± 3.84, 6.32 ± 3.15, 8.24 ± 5.17 and 9.88 ± 2.02, respectively. pREMS accurately predicted hospital discharge and death (AOR = 1.62, P < 0.001) but was not a good predictor of ICU or OR admission (AOR = 1.085, P = 0.603). The AUROCs for the ability of the pREMS to predict outcomes in hospitalized TBI patients were 0.618 (optimal cutoff point = 7) for ICU admission and OR and 0.877 (optimal cutoff point = 9.5) for hospital discharge and death at 72 h. CONCLUSION: The results indicate that the pREMS, a new preclinical trauma score for traumatic brain injury, is a useful tool for prehospital risk stratification (RST) in TBI patients. The pREMS showed good discriminatory power for predicting in-hospital mortality within 72 h in patients with traumatic brain injury.

ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.

The centrality of amyloid-beta (Aß) is an indisputable tenet of Alzheimer's disease (AD). It was initially indicated by the detection (1991) of a mutation within Aß protein precursor (AßPP) segregating with the disease, which served as a basis for the long-standing Amyloid Cascade Hypothesis (ACH) theory of AD. In the intervening three decades, this notion was affirmed and substantiated by the discovery of numerous AD-causing and AD-protective mutations with all, without an exception, affecting the structure, production, and intraneuronal degradation of Aß. The ACH postulated that the disease is caused and driven by extracellular Aß. When it became clear that this is not the case, and the ACH was largely discredited, a new theory of AD, dubbed ACH2.0 to re-emphasize the centrality of Aß, was formulated. In the ACH2.0, AD is caused by physiologically accumulated intraneuronal Aß (iAß) derived from AßPP. Upon reaching the critical threshold, it triggers activation of the autonomous AßPP-independent iAß generation pathway; its output is retained intraneuronally and drives the AD pathology. The bridge between iAß derived from AßPP and that generated independently of AßPP is the neuronal integrated stress response (ISR) elicited by the former. The ISR severely suppresses cellular protein synthesis; concurrently, it activates the production of a small subset of proteins, which apparently includes components necessary for operation of the AßPP-independent iAß generation pathway that are absent under regular circumstances. The above sequence of events defines "conventional" AD, which is both caused and driven by differentially derived iAß. Since the ISR can be elicited by a multitude of stressors, the logic of the ACH2.0 mandates that another class of AD, referred to as "unconventional", has to occur. Unconventional AD is defined as a disease where a stressor distinct from AßPP-derived iAß elicits the neuronal ISR. Thus, the essence of both, conventional and unconventional, forms of AD is one and the same, namely autonomous, self-sustainable, AßPP-independent production of iAß. What distinguishes them is the manner of activation of this pathway, i.e., the mode of causation of the disease. In unconventional AD, processes occurring at locations as distant from and seemingly as unrelated to the brain as, say, the knee can potentially trigger the disease. The present study asserts that these processes include traumatic brain injury (TBI), chronic traumatic encephalopathy, viral and bacterial infections, and a wide array of inflammatory conditions. It considers the pathways which are common to all these occurrences and culminate in the elicitation of the neuronal ISR, analyzes the dynamics of conventional versus unconventional AD, shows how the former can morph into the latter, explains how a single TBI can hasten the occurrence of AD and why it takes multiple TBIs to trigger the disease, and proposes the appropriate therapeutic strategies. It posits that yet another class of unconventional AD may occur where the autonomous AßPP-independent iAß production pathway is initiated by an ISR-unrelated activator, and consolidates the above notions in a theory of AD, designated ACH2.0/E (for expanded ACH2.0), which incorporates the ACH2.0 as its special case and retains the centrality of iAß produced independently of AßPP as the driving agent of the disease.

Metabolomics in severe traumatic brain injury: a scoping review.

BACKGROUND: Diagnosis and prognostication of severe traumatic brain injury (sTBI) continue to be problematic despite years of research efforts. There are currently no clinically reliable biomarkers, though advances in protein biomarkers are being made. Utilizing Omics technology, particularly metabolomics, may provide new diagnostic biomarkers for sTBI. Several published studies have attempted to determine the specific metabolites and metabolic pathways involved; these studies will be reviewed. AIMS: This scoping review aims to summarize the current literature concerning metabolomics in sTBI, review the comprehensive data, and identify commonalities, if any, to define metabolites with potential clinical use. In addition, we will examine related metabolic pathways through pathway analysis. METHODS: Scoping review methodology was used to examine the current literature published in Embase, Scopus, PubMed, and Medline. An initial 1090 publications were identified and vetted with specific inclusion criteria. Of these, 20 publications were selected for further examination and summary. Metabolic data was classified using the Human Metabolome Database (HMDB) and arranged to determine the 'recurrent' metabolites and classes found in sTBI. To help understand potential mechanisms of injury, pathway analysis was performed using these metabolites and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. RESULTS: Several metabolites related to sTBI and their effects on biological pathways were identified in this review. Across the literature, proline, citrulline, lactate, alanine, valine, leucine, and serine all decreased in adults post sTBI, whereas both octanoic and decanoic acid increased. Hydroxy acids and organooxygen compounds generally increased following sTBI, while most carboxylic acids decreased. Pathway analysis showed significantly affected glycine and serine metabolism, glycolysis, branched-chain amino acid (BCAA) metabolism, and other amino acid metabolisms. Interestingly, no tricarboxylic acid cycle metabolites were affected. CONCLUSION: Aside from a select few metabolites, classification of a metabolic profile proved difficult due to significant ambiguity between study design, sample size, type of sample, metabolomic detection techniques, and other confounding variables found in sTBI literature. Given the trends found in some studies, further metabolomics investigation of sTBI may be useful to identify clinically relevant metabolites.

Sex-Specific Alterations in Inflammatory MicroRNAs in Mouse Brain and Bone Marrow CD11b+ Cells Following Traumatic Brain Injury.

Sex is a key biological variable in traumatic brain injury (TBI) and plays a significant role in neuroinflammatory responses. However, the molecular mechanisms contributing to this sexually dimorphic neuroinflammatory response remain elusive. Here we describe a significant and previously unreported tissue enrichment and sex-specific alteration of a set of inflammatory microRNAs (miRNAs) in CD11b+ cells of brain and bone marrow isolated from naïve mice as well as mice subjected to TBI. Our data from naïve mice demonstrated that expression levels of miR-146a-5p and miR-150-5p were relatively higher in brain CD11b+ cells, and that miR-155-5p and miR-223-3p were highly enriched in bone marrow CD11b+ cells. Furthermore, while miR-150-5p and miR-155-5p levels were higher in male brain CD11b+ cells, no significant sexual difference was observed for miR-146a-5p and miR-223-3p. However, TBI resulted in sex-specific differential responses of these miRNAs in brain CD11b+ cells. Specifically, miR-223-3p levels in brain CD11b+ cells were markedly elevated in both sexes in response to TBI at 3 and 24 h, with levels in females being significantly higher than males at 24 h. We then focused on analyzing several miR-223-3p targets and inflammation-related marker genes following injury. Corresponding to the greater elevation of miR-223-3p in females, the miR-223-3p targets, TRAF6 and FBXW7 were significantly reduced in females compared to males. Interestingly, anti-inflammatory genes ARG1 and IL4 were higher in females after TBI than in males. These observations suggest miR-223-3p and other inflammatory responsive miRNAs may play a key role in sex-specific neuroinflammatory response following TBI.

Anisocoria without extraocular muscle impairment due to moderate traumatic brain injury with midbrain contusion: a case report.

BACKGROUND: New-onset anisocoria is an important clinical clue to life-threatening intracranial injury. Anisocoria alone without impairment of extraocular muscles is a rare presentation of moderate traumatic brain injury (TBI). CASE PRESENTATION: A 79-year-old woman was transported to hospital soon after falling off a bicycle. Glasgow Coma Scale score on arrival was 11 (E3V3M5). On examination at admission, she was found to be drowsy. Bruising was seen around the right eye and pupil diameters differed (right, 4.5 mm; left, 3.0 mm; both reactive to light). Computed tomography of the head revealed hemorrhagic contusion in the left temporal lobe and left pretectal area of the midbrain, right clavicular fracture, and pulmonary contusion with fractures of the 3rd and 4th ribs. Magnetic resonance imaging confirmed hemorrhagic contusion of the midbrain. The patient achieved full recovery of motor and mental functions with conservative treatment and was discharged on hospital day 17. CONCLUSION: We encountered a case of anisocoria without major extraocular muscle impairment due to moderate TBI with midbrain contusion.

Coding and long non-coding gene expression changes in the CNS traumatic injuries.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are two main central nervous system (CNS) traumas, caused by external physical insults. Both injuries have devastating effects on the quality of life, and there is no effective therapy at present. Notably, gene expression profiling using bulk RNA sequencing (RNA-Seq) and single-cell RNA-Seq (scRNA-Seq) have revealed significant changes in many coding and non-coding genes, as well as important pathways in SCI and TBI. Particularly, recent studies have revealed that long non-coding RNAs (lncRNAs) with lengths greater than 200 nucleotides and without protein-coding potential have tissue- and cell type-specific expression pattern and play critical roles in CNS injury by gain- and loss-of-function approaches. LncRNAs have been shown to regulate protein-coding genes or microRNAs (miRNAs) directly or indirectly, participating in processes including inflammation, glial activation, cell apoptosis, and vasculature events. Therefore, lncRNAs could serve as potential targets for the diagnosis, treatment, and prognosis of SCI and TBI. In this review, we highlight the recent progress in transcriptome studies of SCI and TBI and insights into molecular mechanisms.

Do Vascular and Extracellular Measurements Consistently Reflect Intracellular pO2?

Oxygen measurements are routinely made either in the vasculature or in the extracellular fluid surrounding the cells of tissues. Yet, metabolic oxygen availability depends on the pO2 within the cells, as does the enhancing effect of oxygen on radiotherapy outcomes. This article reports quantitative modeling work examining the effect of cellular plasma membrane composition on tissue permeability, as a window into tissue oxygen gradients. Previous application of the model indicates that lipid-mediated diffusion pathways accelerate oxygen transfer from capillaries to intracellular compartments and that the extent of acceleration is modulated by membrane lipid and protein composition. Here, the effects of broken intercellular junctions and increased gap size between cells in the model are addressed. The conclusion is reached that the pO2 gradient will likely be consistent among similar, healthy tissues but may increase with increased interstitial fluid fraction and broken intercellular junctions. Therefore, tissue structural changes in tumors and other diseased or damaged tissues may lead to aberrations in permeability that confound interpretation of extracellular oxygen measurements.

Intimate partner violence and brain imaging in women: A neuroimaging literature review.

PRIMARY OBJECTIVE: Despite a high prevalence of intimate partner violence (IPV) and its lasting impacts on individuals, particularly women, very little is known about how IPV may impact the brain. IPV is known to frequently result in traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). In this overview of literature, we examined literature related to neuroimaging in women with IPV experiences between the years 2010-2021. RESEARCH DESIGN: Literature overview. METHODS AND PROCEDURES: A total of 17 studies were included in the review, which is organized into each imaging modality, including magnetic resonance imaging (structural, diffusion, and functional MRI), Electroencephalography (EEG), proton magnetic resonance spectroscopy (pMRS), and multimodal imaging. MAIN OUTCOMES AND RESULTS: Research has identified changes in brain regions associated with cognition, emotion, and memory. Howeverto date, it is difficult to disentangle the unique contributions of TBI and PTSD effects of IPV on the brain. Furthermore, experimental design elements differ considerably among studies. CONCLUSIONS: The aim is to provide an overview of existing literature to determine commonalities across studies and to identify remaining knowledge gaps and recommendations for implementing future imaging studies with individuals who experience IPV.