Neurological Research最新文献

Objectives: To improve management of neonatal diseases associated with oxidative stress by introducing advanced diagnostic methods integrating clinical, biochemical, and ultrasound parameters. The study focused on early detection of microvascular changes in preterm infants at risk of hypoxic-ischemic encephalopathy (HIE) and other brain injuries.

Methods: Sixty-three preterm infants (28-34 weeks GA) with RDS grades 1-3 and hypoxic brain injury, plus 19 control newborns, were studied. Oxidative stress was assessed using serum MDA, TAC, and SOD within 24 hours of life. Cerebral microvascularization was evaluated via a multiparametric ultrasound protocol with Microvascular Imaging (MVI), visualizing basal ganglia and periventricular vessels without contrast.

Results: Basal ganglia vessels were visualized in all infants. Periventricular vessel visualization decreased with severity: absent in infants with grade 3 RDS + GMH - IVH 3-4 + hydrocephalus (r = 0.84, p < 0.001). Highest MDA and lowest TAC/SOD were found in these infants. Positive periventricular visualization predominated in mild-moderate RDS. MVI showed 100% negative predictive value for severe ischemic injury but low positive predictive value (35.7%).

Discussion: MVI enables early, noninvasive detection of microvascular changes related to oxidative stress, reflecting endothelial injury. Basal ganglia perfusion remained preserved due to anastomoses, while periventricular white matter, a watershed region, was more vulnerable. Integrating MVI into neurosonography improves diagnostic precision, informs individualized management, and supports neuroprotective strategies in preterm infants with asphyxia and RDS.

Objectives: This study aimed to explore the correlation between single-nucleotide polymorphisms (SNPs) of miR-23a (rs3745453) and sudden sensorineural hearing loss (SSNHL) in the Chinese Han population.

Methods: This case-control study enrolled 160 adult SSNHL patients and 160 age-matched healthy controls between January 2023 and December 2024. miR-23a expression was quantified via RT-qPCR, with diagnostic performance assessed by receiver operating characteristic (ROC) curve analysis. Polymerase chain reaction and ligase detection reaction (PCR-LDR) were employed to genotype the rs3745453 polymorphisms. Clinical characteristics and genotype distributions were systematically compared, followed by univariate and multivariate logistic regression to evaluate rs3745453's correlation with SSNHL susceptibility.

Results: SSNHL patients exhibited significantly reduced miR-23a levels vs controls (p < 0.001), with ROC analysis confirming strong diagnostic capacity (AUC = 0.8885, sensitivity = 86.25%, specificity = 80%, 95%CI = 0.8523- 0.9248, p < 0.001). rs3745453 GG/GA variants showed intergroup distribution differences (p < 0.05), whereas AA genotypes showed no intergroup divergence. G allele frequency was elevated in patients (p < 0.001), with no A allele variation. miR-23a expression did not differ between AG/GG and AA genotypes in controls. In patients, AG/GG carriers displayed lower miR-23a than AA subgroups (p < 0.05). Univariate and multivariate analysis identified miR-23a downregulation and rs3745453 AG+GG as independent SSNHL determinants (all p < 0.05).

Conclusions: These findings suggest that miR-23a expression levels may serve as an independent diagnostic biomarker for SSNHL, while the miR-23a expression and rs3745453 polymorphism are associated with increased susceptibility to adult-onset SSNHL.

Background: Acute ischemic stroke (AIS) is a leading cause of global morbidity and mortality. Tirofiban, a glycoprotein IIb/IIIa inhibitor, may enhance intravenous thrombolysis outcomes. Updated pooled data are needed to clarify its clinical utility and safety.

Methods: This updated meta-analysis included randomized controlled trials (RCTs) and observational studies comparing IVT plus tirofiban with IVT alone in patients with AIS. Literature was searched in PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception through 15 July 2025. Primary outcome was functional independence (modified Rankin Scale [mRS] 0-2). Secondary outcomes included excellent outcome (mRS 0-1), poor outcome (mRS 3-6) at 90 days, National Institutes of Health Stroke Scale (NIHSS) scores at 24-72 hours and NIHSS scores at 5-7 days. Safety outcomes encompassed symptomatic intracranial haemorrhage (sICH), any intracranial haemorrhage (ICH), bleeding, and 90-day mortality. Data were pooled using a random-effects model in RevMan (Version 5.1.4).

Results: Ten studies (4 RCTs and 6 observational; total n = 1,836) were included. Tirofiban + IVT significantly improved functional independence (RR: 1.18, 95% CI: 1.06-1.30; p = 0.002) and excellent outcomes while reducing poor outcomes. NIHSS scores improved significantly at 24-72 hours (MD =  -0.72, 95% CI: -1.20 to -0.25; p = 0.003), but not at 5-7 days. Other outcomes revealed non-significant results.

Conclusions: Tirofiban combined with IVT in AIS may improve recovery without significantly increasing bleeding or mortality. Further high-quality RCTs are needed to refine its use.

Introduction: Tenecteplase (TNK) is a potential alternative to standard-dose alteplase (ALT) for intravenous thrombolysis in acute ischaemic stroke (AIS), but its safety may vary by dose.

Methods: We conducted a systematic literature search in PubMed, Embase, and CENTRAL through 14 February 2025. Interventions included intravenous TNK at 0.1, 0.25, 0.32, or 0.4 mg/kg versus ALT 0.9 mg/kg. Primary outcomes were all intracranial haemorrhage (ICH) and symptomatic ICH; secondary outcomes included modified Rankin Scale (mRS) 0-1 and 0-2, severe adverse events (SAEs), and mortality. A network meta-analysis was performed using a frequentist random-effects model.

Results: Eleven randomized controlled trials were included. No significant differences were observed between TNK and ALT for all ICH or symptomatic ICH. TNK 0.25 mg/kg and 0.1 mg/kg consistently ranked higher in safety, while TNK 0.4 mg/kg was associated with numerically greater odds of ICH (I² = 73.7% for all ICH; 39.7% for symptomatic ICH). TNK 0.25 mg/kg was superior to ALT for achieving mRS 0-1 (OR 1.14, 95% CI: 1.03-1.27). No significant differences were observed in SAEs or mortality, though TNK 0.4 mg/kg ranked least favorably.

Conclusion: TNK at 0.25 mg/kg may offer the most favorable balance of safety and efficacy for AIS. In contrast, the 0.4 mg/kg dose was associated with increased haemorrhagic risk and lower safety rankings.

Objective: Cerebral edema is a major contributor to mortality in diverse pathologies; regretfully, no effective therapies can reduce the associated damage. In cerebral ischemia, ionic edema formation is mediated by the sulfonylurea receptor 1 (SUR1)/transient receptor potential melastatin 4 (TRPM4) complex expressed in brain endothelial cells. Given that Resveratrol reduces the damage induced in human brain endothelial cells (HBEC-5i) subjected to oxygen-glucose deprivation (OGD)/reoxiygenation (R) by down-regulating SUR1 expression, we aimed to determine whether Resveratrol modulates SUR1-TRPM4 activity in this model.

Methods: HBEC-5i cells were exposed to OGD for 2 h followed by 24 h of R. Intracellular Na⁺ accumulation, measured with the Na-sensitive fluorescence probe coronaNa Green, was used as an indicator of SUR1-TRPM4 activity. Immunofluorescence assays were performed to evaluate SUR1 and TRPM4 expression. Resveratrol (5 μM) was administered during OGD/R. Diazoxide was used to identify responding cells.

Results: Resveratrol reduced the increase in intracellular Na⁺ induced by OGD/R and linked to SUR1/TRPM4 activation. While the basal SUR1 and TRPM4 expression levels were low, OGD/R induced their overexpression. Nonetheless, their intracellular distribution indicated incomplete co-localization. A subset of cells showed Na⁺ elevation after OGD/R, suggesting that although many cells expressed SUR1 and TRPM4, most did not form functional complexes. Diazoxide increased Na⁺ influx exclusively in 'responding' cells, confirming functional SUR1-TRPM4 activity in this subpopulation.

Conclusion: SUR1-TRPM4 becomes functionally expressed in a subset of HBEC-5i during OGD/R and pretreatment with Resveratrol attenuated this response. Early modulation of SUR1-TRPM4 by Resveratrol may represent a potential strategy to limit ionic edema.

Objectives: Aberrant glucose metabolism serves as a hallmark of glioblastoma (GBM). This study aimed to identify biomarkers linked with glycolysis in GBM, thereby providing a theoretical framework for its treatment.

Methods: We retrieved the gene expression profiles from the GSE 50161 dataset, screened differentially expressed genes (DEGs) and key modules through Weighted Gene Co-expression Network Analysis (WGCNA), and ultimately identified the critical gene via protein-protein interaction (PPI) networks, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis. In addition, we employed multifaceted immunological, metabolic, and functional assays to experimentally elucidate the regulatory mechanisms of the critical gene within the context of aberrant glucose metabolism in GBM.

Results: The brown module was the key module for GBM, and 8 critical genes were obtained for ROC analysis. Peroxidasin (PXDN) was identified as the critical gene associated with glycolysis in GBM. In in vitro experiments, elevated PXDN expression in GBM cell lines was quantified through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. PXDN knockdown significantly reduced glycolytic flux and impeded the malignant phenotypes of GBM cells by downregulating lactate dehydrogenase A (LDHA) expression. In vivo experiments demonstrated that PXDN knockdown effectively suppressed GBM growth. Conversely, LDHA overexpression not only promoted these malignant phenotypes and glycolytic capacity but also substantially reversed the tumor-suppressive effects induced by PXDN knockdown.

Discussion: PXDN is identified as a potential diagnostic indicator for GBM, and PXDN promotes malignant progression in GBM by modulating LDHA. Anti-PXDN therapy may represent a viable new approach to combat GBM.

Background: Stroke remains a leading cause of mortality and long-term disability in the Middle East and North Africa (MENA) region. The substantial burden of stroke in low- and middle-income countries, where 75% of stroke-related deaths and 81% of disability-adjusted life years occur, underscores the critical need for region-specific adaptations of acute stroke care guidelines to address critical regional challenges while maintaining evidence-based core principles of care.

Methods: We adapted evidence from multiple international guidelines (AHA/ASA 2019-2023, ESO 2021-2023, NICE 2019-2022, Chinese Stroke Association 2022) and recent meta-analyses using MENA-SINO's systematic seven-step framework including comprehensive evidence review, multidisciplinary expert panel input from 45 experts across 22 MENA countries, regional implementation barrier assessment, and formal modified Delphi consensus procedures achieving > 85% agreement. Recommendations employ modified Class of Recommendation, Level of Evidence, Resource-Limited designations, and Expert Opinion statements following AGREE II standards.

Key recommendations: Our regional roadmap emphasizes ten cornerstone concepts: (1) tiered stroke care systems with telemedicine networks; (2) rapid reperfusion protocols for IV thrombolysis within 4.5 hours and mechanical thrombectomy within 6-24 hours based on imaging; (3) resource-stratified care; (4) culturally sensitive decision-making frameworks; (5) aggressive secondary prevention targeting regional risk factor patterns; (6) standardized quality metrics across diverse systems; (7) comprehensive workforce development programs; (8) appropriate technology integration; (9) region-specific emergency response systems;and (10) sustainable phased implementation strategies.

Conclusion: These guidelines provide the first comprehensive, resource-stratified framework for acute ischemic stroke management across the MENA region, with practical adaptations addressing diverse healthcare settings while preserving essential evidence-based care components.

Objective: To compare morphological features between ruptured and unruptured internal carotid artery siphon aneurysms (ICSA) and identify predictors associated with rupture risk.

Methods: We retrospectively analyzd 156 patients with ICSA-49 with ruptured aneurysms (51 aneurysms) and 107 with unruptured aneurysms (120 aneurysms) - evaluated using volume computed tomographic digital subtraction angiography (VCTDSA). Twenty-one morphological and clinical indices, including aneurysm size, inclination angle and aspect ratio, were compared. Statistical analyses comprised univariate testing, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression.

Results: Univariate analysis revealed significant differences in aneurysm size, morphology, dimensions, angulation parameters, shape indices, maximal diameter, multiplicity and patient age between ruptured and unruptured ICSA (all p < 0.05). ROC curve analysis identified the inclination angle (AUC = 0.730), the inflow angle (AUC = 0.763) and aneurysm size (AUC = 0.755) as strong discriminators of rupture risk. Multivariate logistic regression identified three independent predictors of rupture: aneurysm size (OR = 12.607, 95% CI: 4.400-36.124; p < 0.001), inclination angle (OR = 4.062, 95% CI: 1.570-10.513; p = 0.004), and multiplicity (OR = 4.274, 95% CI: 1.620-11.272; p = 0.003).

Conclusions: Inclination angle, aneurysm size, and multiplicity are key morphological predictors of rupture in ICSA. These findings provide a valuable reference for morphologic assessing aneurysm rupture risk, enhancing clinical risk stratification.

Background: Acute spinal cord injury (SCI) results in irreversible neurological deficits. We hypothesized that local transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with erythropoietin (EPO) would inhibit glial scarring and accelerate functional recovery.

Objective: To quantify the therapeutic efficacy and underlying mechanisms of BMSCs+EPO versus BMSCs alone in a rat model of acute SCI.

Methods: Forty SD rats (T10 Allen 60 g·cm impact) were randomized to sham, SCI, SCI+BMSCs, or SCI+BMSCs+EPO (n = 10). BMSCs (5 μL, 2 × 10⁵ cells μL^-1) were micro-injected into the lesion epicenter at 1 h post-injury; EPO (5 000 IU kg^-1) was given intraperitoneally 1 h after surgery. BBB scores were obtained at 1 d, 2 w and 4 w. Western blot, qPCR, histopathology, immunohistochemistry, ELISA, and in vitro cell viability/CCK-8 assays were performed.

Results: At 4 weeks, BBB scores in the BMSCs+EPO group reached 12.7 ± 1.5, representing a 54% increase over the BMSCs-alone group (8.3 ± 0.7, p = 0.003) and a 179% increase over the SCI group (4.6 ± 0.6, p < 0.001). Combination therapy significantly reduced glial fibrillary acidic protein (GFAP) and vimentin expression, decreased pro-inflammatory cytokines (IL-1β, TNF-α) and chondroitin-sulfate proteoglycans, while elevating BDNF, GDNF and IGF-1 levels. Histological cavitation was reduced by 42% versus BMSCs alone. In vitro, EPO rescued LPS-induced BMSC death, suppressed astrocyte over-proliferation, and promoted PC12 neurite outgrowth via enhanced BDNF/GDNF secretion.

Conclusion: BMSCs+EPO exerts synergistic neuroprotective effects, achieving superior locomotor recovery compared with BMSCs monotherapy, and represents a promising adjuvant strategy for acute SCI.