Search Results (1,408)

(1) Background: Traumatic brain injury (TBI) triggers synaptic loss, leading to long-term neurological deficits. Electroacupuncture (EA) benefits neurological conditions, but its mechanisms after TBI remain unclear. (2) Methods: We used a controlled cortical impact (CCI) mouse model. Behavioral outcomes were assessed using the modified neurological severity score (mNSS), rotarod, Y-maze, and novel object recognition test (NORT). Synaptic morphology was examined by transmission electron microscopy (TEM). Energy metabolism was assessed using biochemical assays, and mitochondrial function was assessed using flow cytometry. Quantitative real-time PCR (qPCR) and Western blotting (WB) were used to examine the underlying molecular mechanisms. (3) Results: We found that EA ameliorates TBI-induced motor and cognitive impairments by preserving synaptic and mitochondrial integrity. EA-treated mice showed improvements in mNSS, rotarod, NORT, and Y-maze performance, along with preserved synaptic ultrastructure and mitochondrial function. CaMKII overexpression abolished EA-induced neuroprotection, identifying the CaMKII/Drp1 axis as a key mediator. (4) Conclusions: Thus, EA limits TBI deficits by restraining CaMKII/Drp1-driven mitochondrial fission and subsequent synaptic loss. Full article

Background: Between 33% and 75% of women who experience intimate partner violence (IPV) sustain an IPV-related traumatic brain injury (TBI). Although IPV-related TBI is associated with adverse psychosocial outcomes, its impact on response to healthcare-based IPV interventions remains unclear. Methods: Using data from a randomized clinical trial within the Veterans Health Administration, we examined psychosocial outcomes among 60 woman veterans with past-year IPV experiences participating in two brief IPV interventions: Enhanced Care As Usual (ECAU) and Recovering from IPV through Strengths and Empowerment (RISE). Results: At pretreatment, 21 women (35%) reported a history of probable IPV-related TBI. Multilevel modeling revealed no significant main or interaction effects of TBI history for self-efficacy, empowerment, patient activation, depression, physical health symptoms, or resilience. However, there was a significant interaction of time and probable IPV-related TBI history for valued living, such that women with probable IPV-related TBI history demonstrated greater initial gains followed by slight posttreatment decline; F(2, 76.55) = 2.96, p = 0.049. There was also a significant interaction between probable IPV-related TBI history, treatment condition, and pretreatment anxiety symptoms for anxiety symptoms as an outcome, such that women with probable IPV-related TBI history in the RISE condition, who had more severe anxiety symptoms at pretreatment, reported higher anxiety symptoms on average across the study period than women without probable IPV-related TBI history in RISE; F(1, 48) = 5.04, p = 0.029. Furthermore, there was a significant interaction of probable IPV-related TBI history and pretreatment physical health symptoms for physical health symptoms as an outcome, such that women with probable IPV-related TBI histories maintained higher physical symptoms from pretreatment to the last follow-up assessment; F(1, 134) = 8.99, p = 0.004. Conclusions: No evidence of differential treatment response was detected for women with and without probable IPV-related TBI history. Findings related to valued living and anxiety suggest areas where additional support may improve implementation of brief healthcare-based IPV interventions. Full article

Traumatic brain injury (TBI) is associated with heterogeneous neurophysiological and behavioral outcomes that are not always captured by conventional clinical classifications. This study aimed to characterize electrophysiological patterns in individuals with TBI and examine their alignment with clinical groupings. EEG, event-related potentials (ERPs), spectral features, and behavioral performance were analyzed in 121 participants from a larger clinical cohort. Data were preprocessed using artifact subspace reconstruction (ASR), adaptive mixture independent component analysis (AMICA), and standardized quality control procedures. Spectral power, ERP components, and behavioral metrics were extracted and compared across clinical severity and OSU TBI-ID classifications, and unsupervised k-means clustering was applied to identify data-driven electrophysiological subgroups. Results demonstrated consistent ERP signal quality across participants, with all datasets meeting P300 global field power thresholds. While group-level comparisons revealed distributions of electrophysiological markers across clinical categories, clustering identified two electrophysiological subgroups characterized by differing spectral, connectivity, and ERP profiles that were not significantly associated with OSU TBI-ID classifications. Electrophysiological subgroup assignments were not significantly associated with OSU TBI-ID classifications. These findings suggest that data-driven electrophysiological subgrouping captures variability not reflected in traditional clinical groupings, highlighting the potential utility of electrophysiological measures for characterizing heterogeneity within chronic TBI populations. Full article

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability worldwide and is frequently associated with persistent impairments in consciousness, cognition, mood, and functional independence. Despite advances in acute neurocritical care, effective therapies that enhance neurological recovery remain limited. Neuromodulation has emerged as a promising strategy to augment neuroplasticity and improve recovery through both pharmacologic and non-pharmacologic approaches. This narrative review summarizes current evidence supporting pharmacologic neuromodulatory therapies, including central nervous system stimulants (methylphenidate and modafinil), dopaminergic agents (amantadine and bromocriptine), acetylcholinesterase inhibitors (donepezil and rivastigmine), and selective serotonin reuptake inhibitors (sertraline and fluoxetine). Mechanisms of action, clinical efficacy, adverse effects, and practical considerations across the acute, subacute, and chronic phases of TBI recovery are discussed. Emerging non-pharmacologic neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation, are also reviewed. Although amantadine remains the only neuromodulator supported by moderate-quality guideline recommendations for accelerating recovery in disorders of consciousness, accumulating evidence suggests that several additional pharmacologic and non-pharmacologic neuromodulation interventions may improve attention, executive function, fatigue, mood, and rehabilitation participation in carefully selected patients. However, current evidence is limited by heterogeneous study populations, small sample sizes, inconsistent outcome measures, and a paucity of long-term randomized controlled trials. Future research should prioritize adequately powered comparative studies, standardized outcome measures, biomarker-guided patient selection, and multimodal treatment strategies to optimize neurological recovery following TBI. Full article

Background: Non-missile penetrating traumatic brain injury (pTBI) is a rare but life-threatening condition. In self-inflicted cases involving the frontal sinus, a rigorous preoperative diagnostic workup is crucial to assess foreign body fragmentation, trajectory, and potential vascular compromise. The complexities of such cases demand a highly structured approach to prevent severe secondary brain injury and long-term infectious sequelae. Case Presentation: A 36-year-old male with schizophrenia presented after attempting suicide by stabbing a kitchen knife through his frontal sinus. Multimodal diagnostic imaging was immediately employed. Skull radiographs and computed tomography (CT) precisely delineated the blade traversing the frontal sinus and entering the anterior cranial fossa. Crucially, given the proximity to the skull base, digital subtraction angiography (DSA) was proactively performed, which confirmed the absence of major cerebrovascular injury and safely guided the surgical strategy. Based on these precise imaging findings, a bifrontal craniotomy was performed. During the procedure, the main blade was extracted, and a retained broken metallic tip—recognized upon close intraoperative inspection of the extracted blade—was successfully retrieved from the intracranial compartment. Postoperative wound infections (with causative pathogens isolated as Serratia odorifera and coagulase-negative Staphylococci) were effectively eradicated with targeted antibiotics. The patient achieved a favorable neurological recovery. Conclusions: Multimodal neuroimaging, particularly the combination of CT and DSA, can be highly beneficial in the diagnostic workup of complex pTBI. Precise preoperative imaging helps guide the optimal surgical approach, ensuring complete foreign body removal and minimizing severe secondary complications. Early intervention, guided by standardized imaging and followed by aggressive medical management, can yield positive outcomes even in severely morbid presentations. Full article

Mild traumatic brain injury (mTBI) is a common cause for pediatric emergency department visits and can impose substantial burdens on families, including missed work and childcare needs. Socioeconomic context may influence both healthcare use and these downstream impacts. This study examined the association between Child Opportunity Index (COI), a neighborhood-level measure of socioeconomic status, and healthcare utilization and indirect costs following pediatric concussion. In a secondary analysis of a multisite randomized controlled trial of patients with acute (<72 h) concussion, participants were categorized into high, middle, and low COI groups. Outcomes included follow-up care, caregiver missed workdays, childcare needs, and indirect costs, analyzed using multivariable regression models. Participants from lower COI neighborhoods were more likely to present to the emergency department, with 93.02% compared to 71.43% in higher COI groups (p = 0.005); had higher symptom scores at 14 days, 28.69 versus 16.64 (p = 0.03); and were less likely to be seen by concussion specialists, 6.98% versus 28.57% (p = 0.005). They also had lower odds of attending follow-up within 14 days (OR = 0.36, p = 0.015) and higher caregiver burden, including more missed workdays and childcare needs. Although total indirect costs did not differ significantly for low COI groups after adjustment, middle COI participants had lower costs than high COI ones. Overall, disparities were observed in care patterns and caregiver burden despite similar recovery outcomes. These findings suggest that expanding access to affordable concussion follow-up through school-based programs, telehealth services, transportation assistance, and flexible scheduling may help reduce caregiver burden and improve continuity of care for children from lower COI neighborhoods following pediatric mTBI. Full article

Background and Objectives: Traumatic brain injury (TBI) is one of the leading causes of long-term disability among adults, with consequences for balance, postural stability, and quality of life. Addressing balance disorders in TBI patients requires a tailored and continuous care approach; the existing literature underlines a general framework for physiotherapy treatments, but no clear profile of technique, dosage and timing of intervention emerges. The present scoping review, therefore, aimed at mapping physiotherapy approaches to balance in TBI population, highlighting their potential effects and role through care pathways. Materials and Methods: A scoping review was conducted, according to PRISMA Extension for Scoping Reviews, with the aim of mapping physical therapy approaches to treat balance disorders in adult patients with TBI. A specific search string for each database was formulated through a PCC (Population, Concept, Context) framework. The search, limited to articles in English and published between 2015 and 2025, was conducted across five databases (PubMed, PEDro, Scopus, Embase, and Web of Science), including experimental studies, observational designs, and `case reports. Results: From the initial selection of 1052 records, six studies were included: five randomized controlled trials and a case report, published between 2016 and 2022. Results presented high heterogeneity of physiotherapy programs and outcome variations; interventions identified included virtual reality, video game therapy, adapted physical exercise, ballistic training, rapid-resistance elliptical training, and rhythmic auditory stimulation. These studies reported variable improvements in balance and mobility, not even with significant inter-group differences. Conclusions: Several techniques showed preliminary evidence in pre/post improvements of balance for TBI patients, including strength exercise, aerobic training and virtual-mediated approaches such as video game therapy and virtual reality. Rhythmic auditory stimulation has unclear effects. Future studies are needed to define the impact of each balance recovery strategy according to the baseline characteristics of the patient. Full article

Background/Objectives: Clinical outcomes after traumatic brain injury (TBI) remain difficult to predict, highlighting the need for more sensitive diagnostic and prognostic biomarkers, particularly in polytrauma. This study aimed to identify TBI-specific proteomic signatures in plasma and extracellular vesicles (EV)-enriched fractions of critically injured trauma patients. Methods: Seventy-five severely injured adult trauma patients (ISS ≥ 16) were included: isolated severe TBI (TBI; AIS_head ≥ 4, other AIS ≤ 1, n = 23), polytrauma with TBI (PT-TBI; AIS_head ≥ 4, n = 22), and polytrauma without TBI (PT; AIS_head = 0, n = 30). 24 age- and sex-matched healthy volunteers served as controls. Neat plasma and EV-enriched fractions were profiled using HPLC-MS/MS. Differentially expressed proteins (DEP) were analyzed bioinformatically, and associations with clinical parameters were assessed using Spearman’s correlation. Results: The EV-enriched plasma fraction yielded more DEPs than neat plasma (846 vs. 258). Most DEPs were linked to polytrauma, with plasma reflecting metabolism and EVs showing translation and protein catabolism signatures. Among TBI-context proteins, EV-associated NRCAM and AQR and plasma IGHV1-69D, MASP1, PON1, and IGFBP7 remained significantly associated with TBI after adjustment for confounder. Notably, only EV-associated proteins correlated with injury-related clinical parameters. AQR negatively correlated with GCS (r = −0.51, p < 0.0001), while elevated NRCAM, AQR, and plasma MASP1 were associated with neurological deterioration and neurosurgical intervention. Conclusions: EV-enriched plasma proteomics enhances biomarker discovery in polytrauma, revealing distinct pathways and greater sensitivity than whole plasma. While most changes reflect systemic injury, EV-associated NRCAM and AQR, along with plasma MASP1, show TBI-specific associations with neurological status, highlighting their potential as candidate TBI biomarkers for further study. Full article

Traumatic subarachnoid hemorrhage (tSAH) is a common complication of traumatic brain injury (TBI) and represents an important predictor of poor functional outcome. One of the most serious secondary complications is cerebral vasospasm. The pathophysiology of vasospasm is complex, involving the effects of blood breakdown products, inflammatory mediators, and direct mechanical injury to the cerebral vessels. Compared to aneurysmal subarachnoid hemorrhage (aSAH), vasospasm in tSAH typically occurs earlier, lasts for a shorter duration, and presents mostly with a milder clinical course. Due to its atypical clinical presentation and the presence of concurrent injuries, vasospasm is often not recognized in time and may manifest as neurological deterioration or new ischemic lesions on CT imaging. Timely recognition and appropriate management can significantly improve neurological outcomes. This paper presents key characteristics and differences between tSAH and aSAH, available diagnostic approaches, and treatment options, including nimodipine, milrinone, and stellate ganglion block. Owing to the lack of specific clinical guidelines for tSAH, current management strategies often rely on recommendations and experiences from aSAH. Further research is needed to better define risk factors for vasospasm following tSAH, optimize diagnostic pathways, and evaluate targeted treatment strategies. Full article

Introduction: Acute subdural hematoma (aSDH) represents one of the most lethal and debilitating forms of traumatic brain injury (TBI) encountered in neurosurgical emergency settings, carrying high mortality rates and severe long-term functional deficits. Historically, the timing of surgical decompression has been considered a critical modifiable prognostic factor. However, contemporary evidence regarding the relationship between time to surgery and clinical outcomes remains inconsistent. This systematic review and meta-analysis evaluates the impact of surgical timing on mortality and functional status in adult patients undergoing evacuation for acute subdural hematoma. Methods: A systematic review was conducted according to the PRISMA 2020 guidelines and registered in PROSPERO. A database search was performed across PubMed, Scopus, Embase and Web of Science for relevant studies published between 2009 and 2026. Peer-reviewed cohort studies and clinical trials including adults (>18 years) with CT- or MRI-confirmed aSDH were included. Data extraction focused on baseline characteristics, surgical timing thresholds, and primary outcomes of mortality and functional status assessed using the Glasgow Outcome Scale (GOS). Methodological quality was assessed using the Newcastle-Ottawa Scale. Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: The search identified 1815 records, of which six studies, including 926 patients, met the inclusion criteria. Meta-analysis found no statistically significant association between time to surgery and mortality (RR 1.01, 95% CI [0.69, 1.48], p = 0.96; RD −0.02, 95% CI [−0.19, 0.15]). High statistical heterogeneity was observed (I² = 80%) across the included cohorts. Most studies indicated that patients who underwent rapid neurosurgical intervention frequently presented with significantly worse baseline neurological status, which acts as a primary confounding factor and drives poorer prognostic trends. Conclusions: While historical paradigms emphasize a 4h period for subdural hematoma evacuation, our meta-analysis indicates that a straightforward linear relationship between time to intervention and improved survival or functional outcome is absent in contemporary clinical studies. Surgical timing thresholds must be interpreted cautiously, as the decision-making process is heavily guided by clinical triage bias, where rapidly deteriorating patients are prioritized for urgent decompression. Crude timing thresholds do not reflect a lack of causal benefit of early intervention but rather highlight the profound confounding by indication embedded in contemporary neurotrauma literature. Future multicenter investigations adjusting for admission severity, pupillary reactivity, associated intracranial pathology and other confounding factors are crucial to isolate the true prognostic value of surgical timing in aSDH. Full article

Background/Objectives: In recent years, the perception of mild traumatic brain injury (mTBI) has significantly changed, which implies the need to revise the approach towards post-injury monitoring. Since post-concussion symptoms may overlap with manifestations of neuroendocrine dysfunction, we investigated whether thyroid hormone measurements may provide complementary information to neuron-specific enolase (NSE), a commonly used biomarker of neuronal injury by assessing the association between NSE and thyroid hormone levels following mTBI and to explore potential neuroendocrine alterations during a 12-month follow-up period. Methods: We conducted a prospective cohort study. Participants, adults aged ≥18 years with mTBI meeting the inclusion criteria, were recruited from a tertiary trauma center emergency department (ED) in northern Poland from January 2023 to October 2025. During their post-head injury admission to the ED, patients had a blood sample taken and were asked to complete online questionnaires. The procedure was repeated after 3, 6 and 12 months. The NSE, pituitary and thyroid hormones were measured using a chemiluminescence immunoassay method (CLIA). The questionnaires used in the study were: Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) and the Polish validation of EQ-5D-5L. Results: Higher NSE levels were associated with lower fT3 levels at 3 months post injury. No significant association was found at 6- and 12-month follow up. Conclusions: In patients with persistently elevated NSE levels three months after mTBI, reduced fT3 concentrations were observed. Although exploratory, these findings suggest a potential link between neuronal injury biomarkers and post-traumatic neuroendocrine responses, supporting further investigation of multi-marker approaches for post-mTBI monitoring. Full article

Pathological states associated with metabolic stress, such as traumatic brain injury (TBI), hypoxia, ischemic stroke, and migraine, are considered elevated risk factors for developing Alzheimer’s disease (AD). However, the mechanism underlying the effect of these conditions on the progression of AD remains largely unknown. Here, we determine how metabolic stress associated with spreading depolarization (SD)—a hallmark of stroke, hypoxia, TBI, and migraine—modulates amyloid β (Aβ42) aggregation kinetics through dynamic changes in extracellular space (ECS). To achieve this, we used ThT fluorescence to determine how the formation of different Aβ42 aggregate species depends on Aβ42 concentrations. Based on this input, we build a multiscale computational framework that integrates volume regulation, including its dependence on neuronal ion homeostasis, and Aβ42 aggregation kinetics. Our model predicts that neuronal swelling during SD accelerates aggregation, where the impact of metabolic stress is highly dependent on the timing relative to aggregation progression and the initial monomer concentration. At low monomer concentrations, early SD events promote off-pathway oligomer formation, while at higher concentrations they rapidly drive fibril formation to saturation. In the absence of mature fibrils, recurrent metabolic stress events further amplify oligomer accumulation, whereas pre-existing fibril nuclei suppress oligomer formation at the expense of fibril nucleation and growth. Increasing the intensity of metabolic stress prolongs ECS shrinkage and enhances oligomer formation. These findings reveal a mechanistic link between SD-induced microenvironmental changes and Aβ aggregation dynamics, providing a quantitative framework for understanding how acute brain injury and metabolic stress may contribute to early AD pathogenesis. Full article

Background and Objectives: Mild traumatic brain injury (mTBI) is a common cause of emergency department visits worldwide. Optimal decisions are essential for optimizing patient outcomes while minimizing unnecessary imaging. The present study explores the potential utility of ChatGPT-5.1 for predicting intracranial injury and determining CT necessity in mTBI. Methods: We evaluated adult patients with mild traumatic brain injury who met Canadian CT Head Rule (CCHR) criteria and underwent CT imaging during a two-year period. ChatGPT-5.1 was prompted under two frameworks: ER physician simulation and rule (literature)-based. Additionally, a probabilistic multi-variable logistic regression model was developed. ChatGPT-5.1’s performance was compared with that of human controls (consultants and residents) and the CCHR. Pairwise comparisons were conducted using McNemar’s test. Results: A total of 127 patients were included. ChatGPT-5.1’s recommendation for CT showed comparable performance to CCHR. For predicting CT findings, the probabilistic model achieved the highest performance (accuracy 74.0%), followed by consultants (accuracy 69.3%) and residents (66.9%). The rule (literature)-based model displayed the highest sensitivity (91.8%) but exhibited low specificity (22.2%), indicating a high rate of false positives despite its potential utility as a screening or decision-supporting tool. The ER physician simulation model demonstrated the lowest overall performance (accuracy 54.3%). Statistically significant differences were observed between the probabilistic model and both the ER physician and rule-based models (p < 0.05). Consultants outperformed the ER simulation model (p = 0.01), while their performance was similar to that of the probabilistic model (p = 0.44). Conclusions: ChatGPT-5.1 demonstrated performance comparable to the Canadian CT Head Rule in predicting the need for head CT imaging but showed lower accuracy in identifying intracranial injury. While the literature-based rule model achieved high sensitivity, its low specificity emphasizes that it acts primarily as a conservative screening aid rather than a definitive diagnostic tool in CCHR-positive mTBI patients. Full article

Traumatic brain injury (TBI) disrupts brain metabolism, which evolves over time and varies with the severity of the injury. Monitoring these metabolomic changes may reveal biomarkers indicating early damage, mechanisms of injury, and potentially help predict outcomes. This study used untargeted plasma metabolomics to investigate systemic time-dependent metabolic changes in mice exposed to controlled cortical impact (CCI) with or without replacement of a modified skull cap designed to reduce compensatory space for cerebral edema modelling a severe closed skull TBI, compared to sham controls. Male mice were subjected to CCI, CCI + CAP, or sham procedures comprised a scalp incision or a craniotomy. Plasma samples were collected at 4, 8, and 16 h, and 3 and 7 days after injury. Hydrophilic interaction liquid chromatography–mass spectrometry (HILIC-MS) was used to profile metabolites in all groups and time points, while ion-pair liquid chromatography–mass spectrometry (RPIPLC-MS) was used in CCI and sham mice at the early time points. The largest metabolic changes occurred at 8 h post-injury, distinguishing mice with CCI from sham controls. The early changes concerned metabolism of amino acids, energy, and nucleotide pathways, with metabolites such as succinate, phenylalanine, and cytidine showing significant changes. By 7 days, the metabolic patterns of the injured mice, especially CCI mice, had partially converged toward the sham state, although oxidative and mitochondrial disturbances persisted. The CCI + CAP mice had more pronounced and persistent metabolic disturbances compared to the CCI mice, which may reflect the effect of increased intracranial pressure post-injury. Plasma metabolomics can efficiently capture the evolving biochemical effects of TBI. The findings identified circulating metabolites that were associated with progression and severity of brain injury and provide a basis for future translational studies in human TBI. Full article

D-limonene (D-Lim) is a monocyclic monoterpene and the principal component of citrus essential oils; however, the potential mechanisms underlying its neuroprotective effects in traumatic brain injury (TBI) remain incompletely elucidated. By integrating network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation, this study systematically investigated the potential mechanisms through which D-Lim exerts neuroprotective activity. Database analyses and in vivo experiments showed that the anti-inflammatory and neuroprotective effects produced by D-Lim may be related to the p38 MAPK/NF-κB signaling axis and activation of the PI3K/AKT signaling pathway. Molecular docking and RT-PCR experiments indicated interactions between D-Lim and potential target proteins, including Icam1, Kdr, and Dpp4. HE and Nissl staining demonstrated that D-Lim ameliorated TBI-induced neuronal injury. Moreover, D-Lim had no observable effects on major organs and showed no peripheral toxicity, suggesting its favorable applicability for TBI intervention. Following early intervention with D-Lim, the inflammatory response induced by TBI was attenuated, which may be associated with the activation or modulation of the p38 MAPK, PI3K/AKT, and NF-κB p65 signaling pathways. These results indicate a potential acute protective role for D-Lim under prophylactic or early-intervention conditions, provide insights into TBI intervention, and establish a theoretical basis for potential preventive strategies. Full article