Traumatic Brain Injury Research Articles

Synergistic label-free fluorescence imaging and miRNA studies reveal dynamic human neuron-glial metabolic interactions following injury.

Neuron-glial cell interactions following traumatic brain injury (TBI) determine the propagation of damage and long-term neurodegeneration. Spatiotemporally heterogeneous cytosolic and mitochondrial metabolic pathways are involved, leading to challenges in developing effective diagnostics and treatments. An engineered three-dimensional brain tissue model comprising human neurons, astrocytes, and microglia is used in combination with label-free, two-photon imaging and microRNA studies to characterize metabolic interactions between glial and neuronal cells over 72 hours following impact injury. We interpret multiparametric, quantitative, optical metabolic assessments in the context of microRNA gene set analysis and identify distinct metabolic changes in neurons and glial cells. Glycolysis, nicotinamide adenine dinucleotide phosphate (reduced form) and glutathione synthesis, fatty acid synthesis, and oxidation are mobilized within glial cells to mitigate the impacts of initial enhancements in oxidative phosphorylation and fatty acid oxidation within neurons, which lack robust antioxidant defenses. This platform enables enhanced understanding of mechanisms that may be targeted to improve TBI diagnosis and treatment.

Functional Vision Questionnaire Detects Near Triad Impairments in Adolescent Athletes With Concussion History.

Concussions are mild traumatic brain injuries that often cause vision problems. They have significant impacts on everyday life, cognitive capacity, and sports performance, and may affect injury prevalence in fast contact sports such as ice hockey. A functional vision questionnaire specifically designed for sports was used here to study the correlation between vision problems and concussion history. In this national cross-sectional concussion study, 860 Finnish elite-level male adolescent ice hockey players (aged 13-21 years) answered a functional vision questionnaire and performed a computerized neurocognitive test, ImPACT. Totally 265 athletes reported a history of at least 1 concussion. All data were statistically compared with age-matched athletes with no concussion history (n = 595). For further analysis, athletes were divided into subgroups by age and number of previous concussions. Previously concussed athletes reported more general and eye-specific symptoms than their healthy controls. Increases in eye fatigue, frontal headaches, and blinking were statistically significant. Also statistically more problems with depth perception and evaluating distances, concentration problems, blurred vision, and losing the object in sight were observed among athletes with concussion history. Concussion history reflects an increase in the prevalence of vision deficits, as determined by multiple disturbances in the near triad. The significant number of vision problems in the concussion history groups strongly suggests that functional vision should routinely be evaluated in athletes. The vision problems observed in the athletes with concussion history may indicate an increased injury risk that should be addressed.

Robert (Bob) T. Fraser (1946-2023).

This article memorializes Robert (Bob) T. Fraser (1946-2023), a dedicated advocate for people with disabilities. Bob's contributions were prolific; he authored or coauthored more than 140 peer-reviewed journal articles and book chapters and coedited five texts. He was awarded Federal grants by the National Institute on Disability, Independent Living, and Rehabilitation Research, the Rehabilitation Services Administration, and the Centers for Disease Control and Prevention. Bob was an integral part of a Traumatic Brain Injury Model Systems research team, specializing in outcomes and cost efficacy of return-to-work interventions (e.g., one-to-one placement, supported employment, and paid coworker as trainer) following moderate-to-severe traumatic brain injury. Highlights of Fraser's career and professional contributions are noted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Normative Ranges for Oculomotor and Reaction Time Tests in U.S. Military Service Members and Veterans.

Oculomotor and reaction time tests are frequently used assessments of vestibular symptoms, traumatic brain injury (TBI), or other neurological disorders in both clinical and research contexts. When interpreting these tests it is important to have a reference interval (RI) as a comparison for what constitutes a typical/expected response; however, the current body of research has only limited information regarding normative ranges calculated according to established standards or for a military-specific sample. The purpose of the present study was to describe RIs for oculomotor and reaction time tests in a cohort of service members and veterans (SMVs) for use as comparators by clinicians and scientists. Descriptive. Participants were prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury Study. Only SMVs without a history of TBI or blast exposure were included in the RI calculations. The test paradigms included in this analysis were: smooth pursuit, prosaccades, antisaccades, saccades and reaction time, predictive saccades, optokinetic nystagmus, auditory reaction time, and visual reaction time. Nonparametric methods, based on the U.S. Food and Drug Administration's recognized consensus standards, were used to calculate 95% RIs. A comparison between the calculated RIs and those available from previously published research is provided. Summary statistics and RIs were calculated for 47 outcome parameters from 13 oculomotor and reaction time tests. Sample sizes and age ranges varied across outcome parameters depending on the availability of reference values for RI calculations. The sample sizes used to calculate RIs ranged from 51 to 69. The age of SMVs included in each RI ranged from 19 to 61 years with mean ages ranging from 37 to 39 years. Similarities/differences between the RIs in the present study and those in previously published research are highly dependent on the outcome parameter; however, in general, the RIs in the present study tended to be somewhat wider. The RIs provided in this paper can serve as comparisons for clinicians and scientists who are utilizing these oculomotor and reaction time testing paradigms in similar cohorts of patients or research participants.

Beyond the AJR: Can MRI Predict Outcomes in Children With Severe Traumatic Brain Injury?

Beyond the AJR: Can MRI Predict Outcomes in Children With Severe Traumatic Brain Injury?

Inflammatory Signaling Induces Mitochondrial Dysfunction and Neuronal Death in Traumatic Brain Injury via Downregulation of OXPHOS Genes.

Traumatic brain injury (TBI) is a major cause of neurological dysfunction and disability. This study aimed to investigate the transcriptomic changes and the functional consequences in TBI, focusing on the interplay between inflammation and mitochondrial impairment. Brain tissue samples from TBI patients and healthy controls were subjected to RNA-sequencing analysis. Mouse hippocampal HT-22 cells were treated with inflammatory cytokine and the PGC-1α activator ZLN005. Mitochondrial function, oxidative stress, and apoptosis were assessed using Seahorse respirometry, electron microscopy, flow cytometry, and molecular assays. A TBI mouse model was established to evaluate the therapeutic effects of ZLN005. Transcriptome profiling revealed downregulation of mitochondrial oxidative phosphorylation (OXPHOS) genes, particularly those encoded by the mitochondrial genome, along with enrichment of neurodegenerative pathways in TBI patients. Concomitantly, pro-inflammatory signaling pathways showed upregulation. In vitro studies demonstrated that inflammatory cytokine TNF-α treatment impaired mitochondrial respiration, induced oxidative stress and apoptosis in HT-22 cells, which could be rescued by ZLN005-mediated PGC-1α activation and restoration of OXPHOS gene expression. Administration of ZLN005 in the TBI mouse model alleviated neuronal cell death, preserved mitochondrial integrity, normalized OXPHOS gene levels in brain tissues, and improved cognitive function. This study uncovers a mechanistic link between inflammation-induced downregulation of mitochondrial OXPHOS genes and neuronal damage in TBI. Targeting this pathway by activating PGC-1α represents a potential therapeutic strategy for TBI.

Machine Learning Reveals Demographic Disparities in Palliative Care Timing Among Patients With Traumatic Brain Injury Receiving Neurosurgical Consultation.

Timely palliative care (PC) consultations offer demonstrable benefits for patients with traumatic brain injury (TBI), yet their implementation remains inconsistent. This study employs machine learning methods to identify distinct patient phenotypes and elucidate the primary drivers of PC consultation timing variability in TBI management, aiming to uncover disparities and inform more equitable care strategies. Data on admission, hospital course, and outcomes were collected for a cohort of 232 patients with TBI who received both PC consultations and neurosurgical consultations during the same hospitalization. Patient phenotypes were uncovered using principal component analysis and K-means clustering; time-to-PC consultation for each phenotype was subsequently compared by Kaplan-Meier analysis. An extreme gradient boosting model with Shapley Additive Explanations identified key factors influencing PC consultation timing. Three distinct patient clusters emerged: cluster A (n = 86), comprising older adult White women (median 87years) with mild TBI, received the earliest PC consultations (median 2.5days); cluster B (n = 108), older adult White men (median 81years) with mild TBI, experienced delayed PC consultations (median 5.0days); and cluster C (n = 38), middle-aged (median: 46.5years), severely injured, non-White patients, had the latest PC consultations (median 9.0days). The clusters did not differ by discharge disposition (p = 0.4) or inpatient mortality (p > 0.9); however, Kaplan-Meier analysis revealed a significant difference in time-to-PC consultation (p < 0.001), despite no differences in time-to-mortality (p = 0.18). Shapley Additive Explanations analysis of the extreme gradient boosting model identified age, sex, and race as the most influential drivers of PC consultation timing. This study unveils crucial disparities in PC consultation timing for patients with TBI, primarily driven by demographic factors rather than clinical presentation or injury characteristics. The identification of distinct patient phenotypes and quantification of factors influencing PC consultation timing provide a foundation for developing for standardized protocols and decision support tools to ensure timely and equitable palliative care access for patients with TBI.

Development of individualized risk assessment models for predicting post-traumatic epilepsy 1 and 2 years after moderate-to-severe traumatic brain injury: A traumatic brain injury model system study.

Although traumatic brain injury (TBI) and posttraumatic epilepsy (PTE) are common, there are no prospective models quantifying individual epilepsy risk after moderate-to-severe TBI (msTBI). We generated parsimonious prediction models to quantify individual epilepsy risk between acute inpatient rehabilitation for individuals 2 years after msTBI. We used data from 6089 prospectively enrolled participants (≥16 years) in the TBI Model Systems National Database. Of these, 4126 individuals had complete seizure data collected over a 2-year period post-injury. We performed a case-complete analysis to generate multiple prediction models using least absolute shrinkage and selection operator logistic regression. Baseline predictors were used to assess 2-year seizure risk (Model 1). Then a 2-year seizure risk was assessed excluding the acute care variables (Model 2). In addition, we generated prognostic models predicting new/recurrent seizures during Year 2 post-msTBI (Model 3) and predicting new seizures only during Year 2 (Model 4). We assessed model sensitivity when keeping specificity ≥.60, area under the receiver-operating characteristic curve (AUROC), and AUROC model performance through 5-fold cross-validation (CV). Model 1 (73.8% men, 44.1 ± 19.7 years, 76.1% moderate TBI) had a model sensitivity = 76.00% and average AUROC = .73 ± .02 in 5-fold CV. Model 2 had a model sensitivity = 72.16% and average AUROC = .70 ± .02 in 5-fold CV. Model 3 had a sensitivity = 86.63% and average AUROC = .84 ± .03 in 5-fold CV. Model 4 had a sensitivity = 73.68% and average AUROC = .67 ± .03 in 5-fold CV. Cranial surgeries, acute care seizures, intracranial fragments, and traumatic hemorrhages were consistent predictors across all models. Demographic and mental health variables contributed to some models. Simulated, clinical examples model individual PTE predictions. Using information available, acute-care, and year-1 post-injury data, parsimonious quantitative epilepsy prediction models following msTBI may facilitate timely evidence-based PTE prognostication within a 2-year period. We developed interactive web-based tools for testing prediction model external validity among independent cohorts. Individualized PTE risk may inform clinical trial development/design and clinical decision support tools for this population.

Label-free rat brain traumatic penumbra imaging based on multiphoton fluorescence microscopy

Traumatic penumbra (TP) is a region with recoverable potential around the primary lesion of brain injury. Rapid and accurate imaging for identifying TP is essential for treating traumatic brain injury (TBI). In this study, we first established traumatic brain injuries (TBIs) in rats using a modified Feeney method, followed by label-free imaging of brain tissue sections with multiphoton fluorescence microscopy. The results showed that the technique effectively imaged normal and traumatic brain tissues, and revealed pathological features such as extracellular matrix changes, vascular cell proliferation, and intracellular edema in the traumatic penumbra. Compared with normal brain tissue, the extracellular matrix in the TP was sparse, cells were disorganized, and hyperplastic vascular cells emitted higher two-photon excited fluorescence (TPEF) signals. Our research demonstrates the potential of multiphoton fluorescence technology in the rapid diagnosis and therapeutic evaluation of TBI.

Prehospital Trauma Compendium: Vasopressors in Trauma – a Position Statement and Resource Document of NAEMSP

Acutely injured trauma patients may develop shock from several potential mechanisms, including hypovolemic shock from hemorrhage, neurogenic shock from traumatic brain injury (TBI) or spinal cord injury, obstructive shock from tension pneumothorax or pericardial tamponade, or a mix of several of these mechanisms. Regardless of the cause, restoration of adequate perfusion is of critical importance to reduce the morbidity and mortality of trauma patients with shock. Multiple interventions including hemorrhage control, volume resuscitation with intravenous fluids or blood products, and pleural decompression procedures are used to address some of these issues and are discussed elsewhere in the trauma compendium. The prehospital use of vasopressors to augment organ perfusion pressures seems theoretically appealing for settings where trauma patients have hemorrhagic shock that is refractory to volume resuscitation strategies alone, where blood products are not available, in cases of hypoperfusion caused by neurogenic shock, or to address mean arterial pressure (MAP) goals in severe spinal cord injury. The National Association of Emergency Medical Services Physicians (NAEMSP) reviewed the available evidence surrounding the prehospital use of vasopressors in shock related to trauma to develop the following recommendations as supported by the evidence summarized in the subsequent resource document.

Relationship between the amplitudes of cerebral blood flow velocity and intracranial pressure using linear and non-linear approach.

Intracranial pressure (ICP), cerebral blood flow and volume are affected by craniospinal elasticity and cerebrospinal fluid dynamics, interacting in complex, nonlinear ways. Traumatic brain injury (TBI) may significantly alter this relationship. This retrospective study investigated the relationship between the vascular and parenchymal intracranial compartments by analysing two amplitudes: cerebral blood flow velocity (AmpCBFV) and ICP (AMP) during hypocapnia manoeuvre in TBI patients. Twenty-nine TBI patients hospitalised at Addenbrooke's Hospital, whose ICP and CBFV were monitored during mild hypocapnia, were included. A linear metric of the relationship was defined as a moving-window correlation (R) between AmpCBFV and AMP, named RAMP. Nonlinear metrics were based on the Joint Symbolical Analysis (JSA) algorithm, which transforms AmpCBFV and AMP into sequences of symbols ('words') using a binary scheme with word lengths of three. The mean AmpCBFV and AMP were not significantly correlated at baseline (r = -0.10) or during hypocapnia (r = -0.19). However, the RAMP index was significantly higher at baseline (0.64 ± 0.04) compared to hypocapnia (0.57 ± 0.04, p = 0.035). The relative frequency of symmetrical word types (JSAsym) describing the AmpCBFV-AMP interaction decreased during hypocapnia (0.35 ± 0.30) compared to baseline (0.44 ± 0.030; p = 0.004). Our results indicate that while the grouped-averaged AmpCBFV and AMP were not significantly correlated, either at baseline or during hypocapnia, significant changes were observed when using RAMP and JSA indices. Further validation of these new parameters, which reflect the association between the vascular and parenchymal intracranial compartments, is needed in a larger cohort.

Efficacy of biomarkers and imaging techniques for the diagnosis of traumatic brain injury: challenges and opportunities.

Concussion is a pervasive health issue in the present day. Increased prevalence in recent years has indicated a need to improve the current understanding of minor traumatic brain injury (mTBI). Effort has been devoted to understanding the underlying pathophysiology of TBIs, but some mechanisms remain unknown. Potentially lethal secondary effects of concussion include second impact syndrome and chronic traumatic encephalopathy (CTE), introducing long-term considerations for the management of mTBI. Post-concussion syndrome is another long-term consequence of concussion and may be influenced by both neuroinflammation and hormonal imbalances resulting from head trauma. Genetically mutated apolipoprotein E may also contribute to the severity and persistence of concussion symptoms, perhaps even acting as a risk factor for CTE. As it stands, the diagnosis of concussion is nuanced, depending primarily on subjective diagnostic tools that incorporate patient-reported symptoms and neurocognitive tests. Diagnostic tools provide some assistance in concussion diagnosis, but still lack accuracy and inherently leave room for uncertainty. To mitigate some of this uncertainty, considerable research has been devoted to the development of methods to diagnose concussions objectively. Biomarkers such as S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), neurofilament light protein (Nf-L), interleukin-6 (IL-6) and microRNAs (miRNAs) as well as imaging techniques including diffusion tensor imaging (DTI) and blood-oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) show great promise in this regard. This review aims to compile the relevant literature in these areas in the hopes of being used as a reference point for future research regarding concussions.

Surgical outcome after autologous bone chips replacement in depressed skull fractures: a single center experience

BackgroundSurgery for depressed skull fractures (DSFs) is always faced by multiple challenges including ideal timing, defect reconstruction and complications. Few data are available regarding the aesthetic results and patients’ satisfaction following DSFs management.MethodsA prospective non-randomized study included 59 traumatic brain injury (TBI) patients surgically treated for DSFs. Depressed bone fragments were elevated and washed with diluted hydrogen peroxide for 15 min then replaced within a net made of vicryl 0 through edges of the galea. Our objective was to evaluate outcome and patients’ satisfaction of using autologous bone fragments for skull defect reconstruction.ResultsThe mean Glasgow Coma Scale (GCS) score on admission was 14.51 ± 1.237. The mean age was 16.505 ± 12.426 years. DSFs were of compound type in 81.4% with predominance towards the parietal region 54.2%. Associated intracranial pathologies were found in 39.0% of cases. Mean time to surgery was 5.79 ± 9.982 h. Dura was found torn in 19 cases (32.2%). Postoperative complications were encountered in 5 cases (8.5%). The mean hospital stay was 3.61 ± 3.157 days. 96.6% of cases had good discharge outcome. Factors with significant impact on outcome included; admission GCS score (P < 0.001), type of associated pathology (P = 0.006), and venous sinus involvement (P = 0.003). At the end of follow up, 46 patients (82.5%) were satisfied about the aesthetic results, while 10 patients (17.5%) were not satisfied and 9 of them underwent re-surgery for late cranioplasty.ConclusionsUsing autologous depressed bone chips for skull defect reconstruction can be a safe and feasible surgical technique for TBI patients suffering DSFs with good aesthetic results, high patient satisfaction, decreased need for later cranioplasty and consequently low overall management cost.

Identification of novel tau positron emission tomography tracers for chronic traumatic encephalopathy by comprehensive in silico screening and molecular dynamics simulation.

Chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive mild traumatic brain injury, is characterized neuropathologically by abnormal hyperphosphorylated tau accumulation. Early detection of tau deposition in the brain is crucial for the prevention and evaluation of CTE. Positron emission tomography (PET) tracers can image specific proteins, while the optimal PET tracer for CTE tau fibrils remains unidentified. In this study, structure-based virtual screening and CNS PET MPO algorithms were utilized to identify candidates for novel tau PET tracers from 23 000 compounds in the ChemDiv CNS BBB library. A total of 8 μs molecular dynamics simulations were then employed to evaluate their binding affinity and atomic-level interaction with CTE tau protofibrils. The results indicate that V017-7820 (CNS-4), S776-0061 (CNS-12), S567-0465 (CNS-18), and T828-0465 (CNS-25) exhibit higher docking scores and binding free energies with CTE tau protofibrils while also satisfying the fundamental physicochemical properties of PET tracers. Further simulation analyses reveal that CNS-4 has the strongest binding affinity to tau protofibrils among the four compounds. Hydrophobic, π-π stacking, and hydrogen bonding interactions are the primary driving forces for the binding of these compounds to CTE tau protofibrils. In particular, CNS-12 and CNS-25 exhibit more intense hydrophobic and π-π stacking interactions, whereas CNS-4 and CNS-25 exhibit stronger hydrogen bonding interactions. This study identifies promising lead compounds for tau PET tracers and highlights their mechanism of binding to CTE tau protofibrils, which provides new insights for further screening and development of novel PET tracers for CTE diagnosis.

External Validation of the Surgical Intervention for Traumatic Injuries Scale in Children.

The Surgical Intervention for Traumatic Injuries (SITI) scale is intended to predict the likelihood of needing surgical decompression among patients with traumatic brain injury (TBI). We sought to examine the performance of the SITI score to predict likelihood of acute neurosurgical intervention for children with TBI. We conducted a cross-sectional, retrospective, observational study of children diagnosed with TBI as determined by International Classification of Diseases codes, presenting to a single level 1 pediatric trauma center, between June 1, 2003, and May 31, 2018. The main outcome was decompressive craniotomy or craniectomy within 24 hours of arrival. Data for SITI scoring were abstracted by research assistants, and all cases were scored by a physician who was blinded to the outcome. The SITI scale performance was evaluated using receiver operating characteristic curve and by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). There were 656 encounters with TBI, of which 39 (5.9%) underwent surgical decompression. The mean SITI scores were 4.15 for the operative group and 0.40 for the nonoperative group (P < 0.001). A cutoff of 2 or greater for a positive score gave the best performance with a sensitivity of 0.79, specificity of 0.90, PPV of 0.34, and NPV of 0.99. The area under the receiver operating characteristic curve was 0.89 (95% confidence interval, 0.83-0.96). In sensitivity analysis excluding 75 cases with depressed skull fractures, a score of 2 or greater had a sensitivity of 0.96, specificity of 0.91, PPV of 0.31, and NPV of 1.00. The area under the receiver operating characteristic curve was 0.98 (95% confidence interval, 0.97-1.00). A SITI score of less than 2 is associated with nonoperative management. However, clinicians should not be falsely reassured by a low score in patients with depressed skull fractures.

Neuromodulation techniques in traumatic brain injury: a narrative review of the current state.

Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world. Despite significant advances in medical care, many TBI survivors continue to have cognitive, physical, and psychological deficits that have a significant impact on their quality of life. Neuromodulation techniques, which use electrical or magnetic stimulation to modulate brain activity, have shown promise in the treatment of TBI symptoms. The purpose of this narrative review is to provide an overview of the current state of neuromodulation techniques for TBI, such as transcranial magnetic stimulation, transcranial direct current stimulation, deep brain stimulation, and vagus nerve stimulation. This review summarizes the evidence for using these techniques, as well as their potential mechanisms of action and limitations. Additionally, the review discusses future research directions in this field, as well as the possibility of combining neuromodulation techniques with other interventions to improve outcomes for TBI patients.

Pediatric Emergency Medicine Physicians' Perspectives of Concussion in Young Children.

Traumatic brain injury (TBI) during early childhood (before 6 years) is prevalent, accounting for rising rates of emergency department visits. These injuries may lead to postconcussive symptoms, which may be subtle and difficult to diagnose in young children. Inadequate discharge counseling may lead to prolonged duration of symptoms and possible developmental delays. We aimed to explore pediatric emergency medicine (PEM) physicians' perspectives on "concussion" terminology, diagnosis, and management, specifically in a young child with mild TBI. We conducted semistructured interviews using open-ended questions involving a hypothetical scenario. We recruited currently practicing PEM physicians by a snowball sampling method. A research team recorded, transcribed, and analyzed the interviews. Using social constructionism as the philosophical framework, we developed and refined codes and derived themes until reaching thematic saturation. Peer debriefing with an expert collaborator aided with revisions of themes. A single PEM researcher interviewed 13 participants. Three primary themes emerged. Our first theme identified the role of guidelines and tools in the diagnostic workup. Most participants utilized a clinical prediction tool for neuroimaging but no clinical symptom scales. Our second theme described the difficulties and inconsistencies in the approach to diagnosis of concussion, largely due to young age, lack of verbal skills and unreliable examinations. Our last theme focused on the difficulty in providing clear discharge instructions to parents. Many participants described difficulty providing activity restrictions, instead allowing self-modulation, and lack of counseling for educational tasks. Variability exists among PEM physicians in diagnosis and management of concussions in young children. Discomfort with lack of reliability of symptoms and underappreciation of typical early childhood characteristics may account for findings. Educational initiatives, age-appropriate clinical tools and treatment-guided outcomes research are needed to guide PEM physicians in the care of young children with head injuries.

Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges, and future perspectives on transcriptomic profiling.

Single-cell RNA sequencing (scRNA-seq) is a high-throughput transcriptomic approach with the power to identify rare cells, discover new cellular subclusters, and describe novel genes. scRNA-seq can simultaneously reveal dynamic shifts in cellular phenotypes and heterogeneities in cellular subtypes. Since the publication of the first protocol on scRNA-seq in 2009, this evolving technology has continued to improve, through the use of cell-specific barcodes, adoption of droplet-based systems, and development of advanced computational methods. Despite induction of the cellular stress response during the tissue dissociation process, scRNA-seq remains a popular technology, and commercially available scRNA-seq methods have been applied to the brain. Recent advances in spatial transcriptomics now allow the researcher to capture the positional context of transcriptional activity, strengthening our knowledge of cellular organization and cell-cell interactions in spatially intact tissues. A combination of spatial transcriptomic data with proteomic, metabolomic, or chromatin accessibility data is a promising direction for future research. Herein, we provide an overview of the workflow, data analyses methods, and pros and cons of scRNA-seq technology. We also summarize the latest achievements of scRNA-seq in stroke and acute traumatic brain injury, and describe future applications of scRNA-seq and spatial transcriptomics.

Optimal dose of tranexamic acid in traumatic brain injury: Systematic review and network meta-analysis of randomized controlled trials.

Tranexamic acid (TXA) has been used to treat traumatic brain injury (TBI); however, no definitive conclusions have been drawn regarding its effectiveness or dosage. This study evaluated the optimal TXA dose for treating TBI using a network meta-analysis (NMA). Five databases were searched for peer-reviewed randomized controlled trials (RCTs) published from inception to May 2024. The inclusion criteria were as follows: (1) RCTs, (2) patients older than 1 month with TBI, (3) interventions of TXA and control, (4) primary outcomes of mortality and poor neurological outcomes and secondary outcomes of vascular occlusive events, and (5) full-text peer-reviewed articles. Two reviewers independently screened and extracted the data and assessed the risk of bias. Frequency-based NMA was performed using the Grading of Recommendations, Assessment, Development, and Evaluation working-group approach. We included 10 RCTs comprising 11,237 patients with TBI. Placebo showed higher mortality compared with that of a 2-g bolus of TXA (risk ratio, 1.53; 95% confidence interval, 1.08-2.17). Higher mortality was observed with a 1-g bolus of TXA followed by 1-g maintenance TXA compared with that of a 2-g bolus of TXA (risk ratio, 1.44; 95% confidence interval, 1.02-2.03). No significant differences in poor neurological outcomes or vascular occlusive events were observed between the treatment groups. Placebo and a 1-g bolus followed by 1-g maintenance TXA were associated with higher mortality rates than those of a 2-g bolus of TXA. No difference in vascular occlusive events was observed with either treatment, indicating that our NMA recommends 2 g of TXA. However, the data for the 2-g bolus of TXA were from a single study, and further research is needed to draw definitive conclusions. Systematic Review/Meta-Analysis; Level III.

Evaluation of Snowboarding Helmets in Mitigation of the Biomechanical Responses of Head Surrogate

Traumatic brain injury (TBI) during snowboarding sports is a major concern. A robust evaluation of existing snowboarding helmets is desired. Head kinematics (i.e., linear acceleration, angular velocity, angular acceleration) and associated brain responses (brain pressure, equivalent (von Mises) stress, and maximum principal strain) of the head are a predominant cause of TBI or concussion. The conventional snowboarding helmet, which mitigates linear acceleration, is typically used in snow sports. However, the role of conventional snowboarding helmets in mitigating angular head kinematics is marginal or insignificant. In recent years, new anti-rotational technologies (e.g., MIPS, WaveCel) have been developed that seek to reduce angular kinematics (i.e., angular velocity, angular acceleration). However, investigations regarding the performance of snowboarding helmets in terms of the mitigation of head kinematics and brain responses are either extremely limited or not available. Toward this end, we have evaluated the performance of snowboarding helmets (conventional and anti-rotational technologies) against blunt impact. We also evaluated the performance of newly developed low-cost, silica-based anti-rotational pads by integrating them with conventional helmets. Helmets were mounted on a head surrogate–Hybrid III neck assembly. The head surrogate consisted of skin, skull, dura mater, and brain. The geometry of the head surrogate was based on the GHBMC head model. Substructures of the head surrogate was manufactured using additive manufacturing and/or molding. A linear impactor system was used to simulate/recreate snowfield hazards (e.g., tree stump, rock, pole) loading. Following the ASTM F2040 standard, an impact velocity of 4.6 ± 0.2 m/s was used. The head kinematics (i.e., linear acceleration, angular velocity, angular acceleration) and brain simulant pressures were measured in the head surrogate. Further, using the concurrent simulation, the brain simulant responses (i.e., pressure, von Mises stress, and maximum principal strain) were computed. The front and side orientations were considered. Our results showed that the helmets with anti-rotation technologies (i.e., MIPS, WaveCel) significantly reduced the angular kinematics and brain responses compared to the conventional helmet. Further, the performance of the silica pad-based anti-rotational helmet was comparable to the existing anti-rotational helmets. Lastly, the effect of a comfort liner on head kinematics was also investigated. The comfort liner further improved the performance of anti-rotational helmets. Overall, these results provide important data and novel insights regarding the performance of various snowboarding helmets. These data have utility in the design and development of futuristic snowboarding helmets and safety protocols.