Search Results (1,407)

Background/Objectives: Birth asphyxia is a frequent neonatal complication in humans. Its outcome is variable, and the factors underlying this variability remain incompletely understood. Maternal gut microbiome impairment has been proposed as one factor that may influence offspring neurodevelopment, especially when the immature brain is exposed to additional vulnerability such as perinatal asphyxia (PA). Building on our previous maternal microbiome disruption model and on our prior observation that electroencephalography (EEG) reactivity to photic stimulation under deep anesthesia detects functional impairment two months after PA, we assessed whether this reactivity was further impaired after prolonged gestational antibiotic administration and whether probiotics modulated this effect. Methods: Wistar dams received antibiotics, probiotics, antibiotics with probiotics, or control treatment, and offspring underwent PA. Adult EEG reactivity to photic stimulation was assessed during chloral hydrate-induced burst suppression. Burst count reactivity (BCR) was used as the primary event-based readout of stimulus-evoked burst recruitment and was compared with the suppression-ratio-based burst-suppression reactivity index (BSRi). Results: Burst suppression remained reactive to photic stimulation in all groups. BCR was lower after gestational antibiotic treatment than in controls. The magnitude of the effect was attenuated by probiotics coadministration. BSRi showed the same overall pattern. Conclusions: Prolonged gestational antibiotic exposure increased the severity of perinatal asphyxia as measured by EEG reactivity in the adult offspring. The converging BCR and BSRi results support burst-suppression reactivity as a functional neurophysiological readout in this PA model and support further methodological development of EEG reactivity measures for translational studies of hypoxic–ischemic brain injury. Full article

Background: Spasticity is a frequent and disabling complication in patients with prolonged disorders of consciousness (PDOC), yet its prevalence, distribution, evolution, and relationship with recovery of consciousness remain poorly characterized. The aim was to investigate the prevalence, severity, distribution, and evolution of spasticity in PDOC patients undergoing early intensive neurorehabilitation (EIN), and to explore clinical factors associated with spasticity and its relationship with level of consciousness (LOC). Methods: This study was embedded in the nationwide prospective DOCTOR cohort and included 126 PDOC patients admitted for EIN in the Netherlands between 2019 and 2023. Spasticity was assessed at admission and discharge using the Ashworth Scale (AS) across seven bilateral muscle groups. Associations between spasticity, demographic and clinical variables, medication use, nociception, and recovery of consciousness were analyzed. Results: Spasticity was highly prevalent at EIN admission (88%) and discharge (90%), with mostly bilateral and widespread involvement. Elbow flexors, wrist flexors, hip adductors, and knee flexors were most frequently affected. Severe spasticity was present in 19% at admission and 30% at discharge. Spasticity severity correlated positively with pain scores and use of spasmolytics, but not with LOC. No association was found between spasticity at admission and recovery of consciousness. Conclusions: Spasticity is nearly ubiquitous and often progressive in PDOC, even during specialized neurorehabilitation. Its evolution appears independent of recovery of consciousness, underscoring the need to assess and manage spasticity as a distinct clinical entity. Prospective interventional studies are warranted to optimize spasticity treatment in this population. Full article

Elevated intracranial pressure (ICP) is a major determinant of secondary injury and mortality in severe traumatic brain injury (TBI), yet objective markers of decompressive craniectomy (DC) efficacy remain limited. Optic nerve sheath diameter (ONSD), measurable on computed tomography (CT), has emerged as a non-invasive surrogate of ICP. This study evaluated the relationship between perioperative ONSD changes and clinical and surgical parameters in patients undergoing DC. In this retrospective cohort study, 72 patients with severe TBI were included. ONSD was measured on preoperative and early postoperative CT, and the change (ΔONSD) was analyzed in relation to craniectomy surface area and outcomes. DC resulted in a significant reduction in ONSD (6.44 ± 0.88 mm vs. 5.55 ± 0.82 mm, p < 0.001). Larger craniectomy surface areas were associated with greater ΔONSD change (r = −0.31, p = 0.008). ΔONSD was independently associated with in-hospital mortality (OR = 0.12, p = 0.005), with larger reductions associated with improved survival. Additionally, ΔONSD was correlated with shorter hospital stay (ρ = −0.32, p = 0.007). These findings support ΔONSD as a practical imaging biomarker reflecting the physiological response to DC in severe TBI. Full article

Traumatic brain injury (TBI), a major cause of persistent cognitive impairment (CI), increases the long-term risk of developing dementia, including Alzheimer’s disease (AD). To elucidate this association, we systematically reviewed fluid biomarkers linked to post-TBI cognitive outcomes. A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. A total of 29 clinical studies were included, reporting on several biomarkers related to neural injury and repair, AD-like pathology, and inflammation. Among these, neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1, total tau, and glial fibrillary acidic protein (GFAP) were consistently associated with CI and brain atrophy across various TBI severities and stages. Notably, certain biomarkers assessed during the acute phase (within 7 days post-injury), such as brain-derived neurotrophic factor, neuron-specific enolase, and interleukin-1β, showed significant correlations with CI. In contrast, elevated levels of GFAP and NfL measured during the recovery phase (6 months to 8 years post-injury) were significantly associated with TBI-related CI (TBI-CI). The findings also highlighted that axonal injury, glial activation, neuroinflammation, neuronal damage, and degeneration drive TBI-CI, with tau pathology and synaptic dysfunction emerging as potential bridges from TBI to AD. This review underscores the critical temporal dynamics of fluid biomarkers in TBI-CI, revealing that stage-specific biomarker profiles mirror distinct underlying pathophysiological processes. Future longitudinal studies should focus on well-characterized patient subgroups, adopt standardized diagnostic criteria, and integrate fluid biomarkers with neuroimaging and genetic data. Full article

Severe traumatic brain injury (TBI) is a leading cause of mortality and long-term disability in polytrauma (PT) patients, and its clinical outcome remains difficult to predict due to clinical heterogeneity and secondary injury mechanisms. Current diagnostic and prognostic approaches based on clinical assessment and imaging are limited, particularly in PT where neurological evaluation is often impaired. This study aimed to compare plasma- and extracellular vesicle (EV)-associated microRNA (miRNA) signatures in patients with severe TBI and healthy controls to identify their potential as minimally invasive biomarkers and to improve understanding of molecular responses. For profiling circulating miRNAs, blood samples were collected at ≤3 h and at 48 h after admission. In the screening phase, plasma samples of n = 15 patients with severe isolated TBI (Abbreviated Injury Scale [AIS]Head ≥ 4, all other AIS ≤ 1) and n = 15 age- and sex-matched healthy controls were pooled (n = 5/pool) and subjected to next-generation sequencing (NGS). In the following validation phase, n = 25 severely injured trauma patients (Injury Severity Score [ISS] ≥ 16) were enrolled and stratified into PT without TBI (PT; AISHead = 0; n = 13) and isolated TBI (n = 12). Differentially expressed candidate miRNAs identified in the screening phase were validated in individual plasma and EV samples using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Functional enrichment and pathway analyses were performed using miRNet. NGS identified more differentially expressed miRNAs in plasma (ER: 103; 48 h: 65) than in EVs (Emergency Room [ER]: 14; 48 h: 32). Functional enrichment analysis indicated associations with pathways related to cellular stress, senescence, growth factor signaling, transcriptional regulation, and apoptosis. In validation, 12 of 16 plasma and 10 of 15 EV-miRNAs were confirmed as differentially expressed in TBI patients; among these, three plasma and four EV miRNAs differed between TBI and PT. After adjustment, most plasma miRNAs were associated with injury severity rather than group status. EV miRNA profiles showed heterogeneous patterns, with miR-1469 associated with TBI group status in adjusted analysis, while miR-1237-5p was linked to injury severity and other EV miRNAs showed no consistent group-specific effects. Plasma miRNAs mainly correlated with systemic injury markers, whereas EV miR-1469 showed a moderate association with the Glasgow Coma Scale (GCS). Overall, circulating miRNA profiles after injury appear to be predominantly influenced by systemic trauma severity rather than TBI-specific effects. Plasma miRNAs mainly reflected general injury burden, whereas EV-associated miRNAs showed more heterogeneous patterns, with miR-1469 emerging as a candidate associated with TBI after adjustment for clinical covariates. These findings suggest that EV-derived miRNAs, particularly miR-1469, may provide more targeted signals related to brain injury and warrant further investigation. Full article

Traumatic brain injury (TBI) is a prevalent neurological disorder that induces severe neurological dysfunction and markedly reduces quality of life owing to its complex pathophysiology and limited therapeutic options. Conventional pharmacological and surgical interventions show restricted efficacy because of poor blood–brain barrier penetration and inability to address secondary injury cascades. In recent years, hydrogels have shown significant potential for TBI repair due to their superior biocompatibility, high water content, and ability to mimic the native extracellular matrix (ECM). This review systematically examines recent advances in hydrogel applications for TBI therapy, focusing on their roles as drug delivery platforms, stem cell scaffolds, neuroregeneration promoters, inflammation modulators, and angiogenesis facilitators. Particular emphasis is placed on the therapeutic benefits and underlying mechanisms of ECM-derived hydrogels, self-assembling peptide (SAP) hydrogels, stimuli-responsive smart hydrogels, and functionalized multicomponent systems. Current challenges and limitations in hydrogel applications are also discussed, along with future research directions, to provide scientific rationale and practical guidance for precision TBI therapy. Full article

Background/Objectives: Severe hemorrhagic shock progressing to clinical death remains a major cause of mortality and long-term neurological morbidity despite advances in trauma care. While current resuscitation strategies restore circulation, their ability to preserve brain structure and function following global ischemia–reperfusion injury remains limited. Hemorrhagic shock induces widespread neuronal vulnerability, particularly within the hippocampus and prefrontal cortex, contributing to persistent cognitive and behavioral deficits among survivors. Methods: Using a rat model of hemorrhagic shock-induced clinical death, we evaluated whether resuscitation with VBI-1, a phospholipid nanoparticle-based colloid, supports neurological recovery compared with whole blood-based resuscitation. Animals underwent controlled exsanguination to the point of clinical death, followed by rapid intra-arterial reanimation with either shed whole blood or VBI-1. Two phases of study were performed: histological evaluation of tissues 12 h after resuscitation and, in a separate cohort of animals, longitudinal behavioral recovery over 30 days. Histology focused on evaluating neuronal integrity in the hippocampal CA1 region and prefrontal cortex, neuronal functional status, and microglial responses. Sex was analyzed as a biological variable. Results: Resuscitation with VBI-1 is associated with sustained behavioral recovery, with pronounced sex-dependent effects favoring females during the subacute-to-chronic recovery phase. VBI-1 preserved neuronal density, laminar organization, and neuronal functional integrity in ischemia-vulnerable brain regions. This, and neuronal preservation, correlated with hippocampal-dependent working memory performance. Importantly, resuscitation with VBI-1 did not increase microglial density, coverage, or spatial organization, exacerbating the neuroinflammatory burden. Conclusions: These findings demonstrate that phospholipid nanoparticle-based resuscitation confers meaningful neurological recovery following profound circulatory collapse, highlighting the importance of evaluating resuscitation agents based on long-term brain outcomes. Full article

Parkinson’s disease (PD) and acute kidney injury (AKI) are two conditions with increasing prevalence and severe systemic complications and consequences. This research examines the combined neuroprotective and nephroprotective properties of three medicinal plants, Mucuna pruriens (Muc), Moringa oleifera (Mor), and Silybum marianum (SM), in a murine model of PD, AKI, and their comorbid state (PD–AKI), highlighting the role of the PI3K/AKT/mTOR and Nrf2/NF-κB signaling pathways. The mice were grouped as PD, AKI, or PD-AKI, and with or without the herbal pre-treatment, along with their respective controls. Motor impairments were assessed using the rotarod and pole climb assays. Biochemical indicators of renal function, oxidative stress markers, and inflammatory cytokines were quantified in kidney and brain tissues. Assessment of Nrf2, NF-κB, PI3K, AKT, and mTOR expression levels was performed using qRT-PCR. The AKI groups had significant renal impairment (4-fold increase in creatinine and 7.5-fold increase in BUN), oxidative stress (~5.5-fold increase), and increased cytokine levels (~1.5-fold increase), with downregulation of the PI3K/AKT/mTOR (~2-fold decrease) and Nrf2 signaling pathways (~1.8-fold decrease), alongside upregulation of NF-κB (~2.5-fold increase). The PD and PD-AKI groups exhibited significant neuroinflammation (~1.5-fold increase) and redox imbalance (~6-fold increase) in brain tissue, accompanied by motor impairments (1.6 to 4.6-fold decrease). Pre-treatment with Muc, Mor, and SM significantly ameliorated renal impairments (3.5-fold decrease in creatinine and ~5-fold decrease in BUN) and neurological deficits. These findings establish Muc, Mor, and SM extracts as potent, multi-target interventions capable of disrupting the feed–forward cycle of neuro-renal damage. Full article

Background/Objectives: Severe brain injuries generate complex, long-term needs requiring intensive physical, cognitive and relational care. These conditions also profoundly affect families, who often experience emotional distress, uncertainty and a heavy caregiving burden. Although neuro-palliative care is increasingly recognised, the early integration of palliative care for this population remains limited. This study aimed to explore healthcare professionals’ perceptions of the palliative care needs of patients with severe brain injuries and their caregivers and to identify factors that hinder or facilitate early palliative care implementation in specialised settings. Methods: An interpretive qualitative study was conducted using Reflexive Thematic Analysis. Fifteen semi-structured narrative interviews were carried out with healthcare professionals working in specialised hospital units in Northern Italy. Data were analysed inductively through an iterative and reflexive process following Braun and Clarke’s six phases. Methodological rigour and transparency were ensured using the COREQ checklist. Results: Five themes were identified: (1) intensive, individualised patient care needs with complex communication issues; (2) palliative needs centred on dignity, quality of life and early integrated management; (3) caregivers’ involvement and expectation-related difficulties; (4) continuous or anticipatory grief requiring structured psychological support; (5) facilitators and barriers influencing care pathways. Conclusions: Healthcare professionals identify intertwined and evolving palliative care needs in both patients with severe brain injuries and their families. The findings highlight the perceived importance of early, integrated and multidisciplinary neuro-palliative care models focused on dignity, symptom relief and sustained emotional support. Full article

Introduction: This study explored how illness severity scores correspond to hypoxic-ischemic brain injury (HIBI) after cardiac arrest. Methods: This study included cardiac arrest survivors with sufficient data to calculate the Pittsburgh Cardiac Arrest Category (PCAC) and revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST) scores who underwent brain magnetic resonance imaging and cerebrospinal fluid neuron–specific enolase (CSF-NSE) measurement within 6 h after return of spontaneous circulation. The primary outcome was the association of PCAC and rCAST with quantitative brain injury markers assessed using whole brain mean apparent diffusion coefficient (mean ADC), low ADC volume fractions (PV600, 650, and 700), and CSF-NSE. Results: In total, 81 patients were included. PCAC was not significantly associated with CSF-NSE, mean ADC, or PVs. The rCAST score was significantly associated with higher CSF-NSE, lower mean ADC, and higher PV700. The neurologic sub-score of PCAC was independently associated with all evaluated brain injury markers, whereas the systemic sub-score was not. Of the individual rCAST components, anoxic time was independently associated with CSF-NSE, whereas no other single component was associated with these markers. Conclusions: rCAST was significantly associated with degree of HIBI, whereas PCAC was not. The neurologic sub-score of PCAC showed independent associations with HIBI. Full article

Background/Objectives: Intracerebral hemorrhage (ICH) is a severe subtype of stroke characterized by extensive secondary brain injury driven by oxidative stress, inflammation, and progressive neuronal loss, leading to poor neurological outcomes. Thymoquinone, a bioactive compound derived from Nigella sativa, has demonstrated potent antioxidant and neuroprotective properties, but its integrated effects in hemorrhagic stroke remain insufficiently explored. This study aimed to evaluate the antioxidant and neuroregenerative effects of thymoquinone in a rat model of ICH. Methods: Male Wistar rats with experimentally induced ICH were randomized into untreated controls and two treatment groups receiving thymoquinone (150 mg/kg and 250 mg/kg) for three consecutive days. Oxidative injury and antioxidant responses were assessed using membrane blebbing, malondialdehyde (MDA), superoxide dismutase (SOD) activity, and nuclear factor erythroid 2-related factor 2 (NRF2) expression, while neuroprotection was evaluated by neuronal counts in perihematomal tissue. Results: Thymoquinone treatment significantly reduced membrane blebbing and MDA levels, while markedly increasing SOD activity and NRF2 expression in a dose-dependent manner. These biochemical improvements were accompanied by significant preservation of neuronal morphology and increased neuronal survival, with the 250 mg/kg dose showing the strongest effects. Conclusions: In conclusion, thymoquinone confers robust antioxidant and neuroprotective benefits in experimental ICH and represents a promising candidate for mitigating secondary brain injury following intracerebral hemorrhage. Full article

Background: Spasticity significantly impairs functional recovery after severe acquired brain injury. Current management methods predominantly rely on pharmacological interventions, which can cause substantial side effects or require invasive medical procedures in refractory cases. Focal muscle vibration, a noninvasive technique that applies mechanical vibrations to muscle–tendon units and alters spinal and cortical excitability via proprioceptive pathways, has been effective in reducing spasticity in subjects with stroke. However, there is limited data to support focal muscle vibration as a viable option for improving functional recovery in patients with severe acquired brain injury. Objectives: To evaluate the clinical effects of adding focal muscle vibration to standard physiotherapy compared with standard physiotherapy alone in patients with severe acquired brain injury and spastic hypertonia. Methods: Twenty-four patients were randomly assigned to receive focal muscle vibration in addition to standard care (n = 12) or standard care alone (n = 12) for 3 weeks. Assessments were conducted at baseline, immediately after physiotherapy, and 3 weeks after physiotherapy. The outcomes assessed included the Modified Ashworth Scale, Disability Rating Scale, Modified Barthel Index, and three pain measures. Results: A significant reduction in spasticity was observed in the focal muscle vibration group, as indicated by the Modified Ashworth Scale scores (p = 0.014). Disability Rating Scale scores demonstrated a statistically significant decrease in disability ratings at the end of treatment (p = 0.002) and during the follow-up phase (p = 0.002). Between-group comparisons of change scores revealed a statistically significant improvement in disability ratings in the focal muscle vibration group during the treatment phase (p = 0.011). Significant functional gains were noted on the Disability Rating Scale, which persisted at the follow-up evaluation. Conclusions: Focal muscle vibration reduces muscle spasticity and improves functional status in patients with severe acquired brain injury during inpatient rehabilitation. Future studies with larger sample sizes, blinded assessments, and stratified randomization are needed to verify these findings and develop standardized treatment protocols for this underserved population. Full article

Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent thrombus propagation, venous hypertension with blood–brain barrier disruption, and secondary parenchymal brain injury. Comprehensive clinical assessment, including diagnosis and differential diagnosis, disease severity scores, imaging-based metrics, and prognostic scoring systems, enables accurate evaluation and risk stratification. Emerging therapeutic strategies, including direct oral anticoagulants, corticosteroids for selected patients, natural-origin agents, immunomodulatory therapy, endovascular treatment, optic nerve sheath fenestration, and neuromodulation, provide novel and alternative options for the management of CVT. This review provides a comprehensive overview of CVT pathophysiology, clinical assessment tools, and novel therapeutic strategies to guide clinical decision-making and inform future research. Full article

Background: Patients with traumatic brain injury (TBI) are often underfed and frequently experience enteral feeding (EF) intolerance. We examined the association between EF timing, caloric intake and EF intolerance, and mortality. Methods: We retrospectively evaluated adult patients with moderate-to-severe TBI in a tertiary-care ICU. In the first 7 days, we recorded daily caloric intake from EF and the occurrence of EF intolerance—defined as a gastric residual volume > 500 mL or >250 mL with vomiting. Results: Among 298 patients, 210 (70.4%) received early EF. The median 7-day cumulative caloric intake was 7766 kcal for the early EF group (64.7% of caloric requirement) and 2783 kcal (23.1% of caloric requirement) for the late (after 48 h) EF group (p < 0.001). EF intolerance occurred in only 24 patients (8.1%), with no significant difference between the early and late groups. Hospital mortality was 13.8% with early EF versus 30.7% with late EF (p = 0.001), 8.5% with caloric intake ≥ 80% of requirement versus 21.3% with lower caloric intake (p = 0.02) and 50% in patients with EF intolerance versus 16.1% in those without intolerance (p < 0.001). In multivariable logistic regression analysis, early EF was associated with lower mortality (odds ratio 0.326; 95% confidence interval 0.165–0.644), whereas EF intolerance was associated with higher mortality (odds ratio 7.451; 95% confidence interval 2.787–19.922). Conclusions: In patients with moderate-to-severe TBI, early EF was associated with higher caloric intake and lower mortality compared to late EF. EF intolerance was uncommon but strongly associated with higher mortality. Full article

Background/Objectives: Traumatic brain injury (TBI) often results in heterogeneous recovery across cognitive and motor domains. However, the prognostic implications of motor–cognitive imbalance at the time of rehabilitation discharge remain unclear. This study investigated whether discharge patterns of motor–cognitive imbalance are associated with functional outcomes at 1- and 2-year follow-up in individuals with moderate-to-severe TBI. Methods: We conducted a retrospective cohort study using the Traumatic Brain Injury Model Systems (TBIMS) National Database. Adults discharged from inpatient rehabilitation with available Functional Independence Measure (FIM) motor and cognitive subscores were included (n = 8342). Participants were classified as cognitive-dominant, motor-dominant, or balanced based on standardized discrepancies between FIM motor and cognitive scores. Propensity score matching was performed against the balanced group, yielding a matched cohort of 1310 participants. Outcomes included the Disability Rating Scale (DRS), FIM (total and subscales), Glasgow Outcome Scale—Extended (GOSE), and Participation Assessment with Recombined Tools—Objective (PART-O) at 1 and 2 years. Results: The matched cohort included cognitive-dominant (n = 524), motor-dominant (n = 524), and balanced (n = 262) participants with good covariate balance. Compared with the balanced group, the cognitive-dominant group showed lower disability severity (DRS) at 1 year (β = −0.45; 95% CI, −0.81 to −0.09) and 2 years (β = −0.40; 95% CI, −0.78 to −0.03), and higher FIM total scores at both time points. The motor-dominant group demonstrated higher FIM motor scores but lower odds of favorable disability status (DRS ≤ 3) at 2 years (OR = 0.52; 95% CI, 0.31–0.88). GOSE and PART-O outcomes did not differ significantly across groups. Conclusions: Discharge motor–cognitive imbalance patterns were associated with modest but distinct differences in long-term disability severity and functional independence after moderate-to-severe TBI. The direction of imbalance may provide additional prognostic context beyond total functional scores and support domain-targeted post-acute rehabilitation planning. Full article