International Journal of Neuroscience最新文献

Background: To retrieve and summarize the best evidence for frailty management in patients with ischemic stroke during the rehabilitation period, providing reference for clinical practice.

Methods: The system searches for literature on stroke frailty management in domestic and foreign databases and guideline websites, with a search period from the establishment of the database to November 2024. Two researchers independently evaluated the quality of the literature and organized and summarized the evidence.

Results: A total of 22 articles were included, 4 guidelines, 1 expert consensus, 7 systematic reviews, 1 evidence summary, 1 quasi-experimental study and 8 randomized controlled trials. Finally, 31 pieces of evidence were summarized from six aspects: frailty assessment, team building, exercise intervention, nutritional support, psychosocial support and health education.

Conclusions: The best evidence summary for frailty management in stroke patients is comprehensive, and medical staff should combine clinical application evidence to effectively improve patient frailty.

Aim: To synthesize the mechanistic cascade of secondary injury after traumatic brain injury (TBI) and evaluate emeging drug delivery systems (DSS)in the context of translational therapeutic development.

Methods: This review integrates evidence on secondary injury mechanisms-inclding blood-brain barrier disruption, excitotoxicity, neuroinflammation, oxidative stress, mitochondrial dysfunction, and cerebral edema. Animal models were assessed for reproducibility and biomechanical relevance. Emerging DDS (including liposomes, injectable hydrogels, polymeric nanoparticles, extracellular vesicles, and inorganic nanoformulations) were compared regarding strengths, limitations, safety concerns, manufacturability, and clinical feasibility. Translational barriers and lessons from failed trials were analyzed to propose a mechanism-linked delivery framework.

Results: Secondary injury mechanisms are dynamically interconnected, offering multiple therapeutic targets, but animal model variability limits reproducibility. Each DDS platform demonstrates distinct advantages and limitations in biocompatibility, targeting, and scalability. Despite preclinical promise, clinical translation remains challenging due to poor model fidelity, insufficient pharmacokinetic data, and misalignment between injury mechanisms and delivery strategies.

Conclusion: Links secondary injury mechanisms with rationally designed DDS may improve translation outcomes. Enhancing preclinical riogr and aligning formulation strategies with pathophysiological targets are critical for developmenting effective TBI therapies.

Purpose: To have an insight into language-related functional connectivity in post-stroke aphasia (PSA) from graph theory measurements when performing an ability-matched auditory-verbal task fMRI.

Methods: Fifty-seven PSA patients were stratified into high-level (n = 22) and low-level (n = 35) groups using an ability-matched auditory-verbal fMRI paradigm. Functional connectivity was modeled via ROI-to-ROI generalized psychophysiological interactions, from which graph metrics for predefined language nodes were extracted. Network measure differences were assessed via ANCOVA, followed by binary classification with nested cross-validation. Performance (accuracy, sensitivity, specificity, AUC) and model interpretability (SHAP) were evaluated for the best-performing model.

Results: Random Forest classification reached a significant AUC of 0.671 (p = 0.035, 95%CI [0.512, 0.816]) and an accuracy of 0.667, outperforming other models in analyzing task-embedded resting-state data. Notably, the model demonstrated high sensitivity (0.800) in identifying task levels. SHAP analysis revealed that the left temporo-occipital inferior temporal gyrus (toITG_L) and the right posterior supramarginal gyrus (pSMG_R) were the most influential predictors. High-level task was characterized by increased Local Efficiency in the bilateral pSMG and decreased Global Efficiency in the toITG_L.

Conclusions: Our findings suggest that the high-level group relies on a synergistic interaction between the ventral stream (toITG) and the dorsal stream (pSMG). The shift toward increased local specialization, particularly the compensatory recruitment of the right pSMG, highlights a critical neural modularity strategy for functional recovery. These results suggest the feasibility of integrating graph metrics with interpretable machine learning, offering preliminary insights that could support the development of objective tools for monitoring aphasia rehabilitation.

Alzheimer's disease (AD) is the leading cause of dementia, typically affecting the elderly. It results in cognitive and memory loss with progression that can lead to death. Although the exact cause remains unclear, it is believed to involve genetics, diet and environment. One key sign of AD is the shrinkage of the hippocampus and frontal lobe cortex. MRI is frequently used to diagnose AD due to its ability to capture detailed images of soft tissues. This study proposes an innovative Multi-head Parallel LeNet5-based Alzheimer's Disease Classification (MPL5-ADC) framework. The proposed MPL5-ADC system processes MRI images through several key steps. First, the Modified Wiener Filter (MWF) is applied for noise reduction during preprocessing. Next, Pyramid Convolutional Kernels-based SegNet (PCK-SgN) performs segmentation to isolate relevant brain regions. In the feature extraction phase, Improved Local Gabor Binary Pattern Histogram Sequence (ILGBPHS), shape features and deep features from VGG16 and ResNet are used to capture both texture and structural details. These features are augmented and then input into a Multi-head Parallel LeNet-5 (MPL5) classifier, which produces the final classified output for accurate and early detection of AD. The MPL5-ADC model predicts a higher accuracy score of 98% to confirm that it more consistently classifies Alzheimer's disease using MRI.

Background: Press needle therapy, may alleviate depressive-like behaviors.

Methods: Male rats were randomly allocated into four groups (n = 8): Normal control group (CON), Chronic Unpredictable Mild Stress(CUMS) group (CUMS), Press-needle group (PN), and Fluoxetine group (FLX). A depressive-like model was established by the CUMS paradigm for 28 consecutive days. Body weights were recorded at baseline and on Days 7, 14, and 28. Behavioral assessments were conducted, including: open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT). Protein expression levels of BDNF, CREB, TrkB, AKT, PKA, 5-HT1A receptor, and 5-HT2C receptor in hippocampal tissues were quantified by Western blot analysis. Concurrently, enzyme-linked immunosorbent assay (ELISA) measured the concentrations of PI3K and AKT in hippocampal homogenates, and IL-6 and TNF-α in both hippocampal homogenates and serum samples. Hippocampal mRNA expression levels of 5-HTT, 5-HT1A receptor, TrkB, MAPK, and BDNF were determined using quantitative real-time polymerase chain reaction (RT-qPCR). For morphological assessment, hematoxylin and eosin (H&E) staining was performed on paraffin-embedded hippocampal sections.

Results: Press-needle ameliorated depressive-like behaviors in CUMS-exposed rats, restored body weight gain and improved behavioral performance. The treatment upregulated the hippocampal BDNF/TrkB/CREB signaling pathway, increasing BDNF, TrkB, CREB, AKT, and PI3K in the hippocampus. The therapy modulated serotonergic neurotransmission by increasing hippocampal 5-HTT expression, while downregulating 5-HT1A and 5-HT2C receptors and PKA. Notably, press-needle exerted anti-neuroinflammatory effects, reducing hippocampal and serum levels of TNF-α and IL-6. Histopathological analysis confirmed its neuroprotective efficacy, demonstrating attenuated neuronal damage in hippocampal tissues.

Background: Epilepsy is a multifactorial neurological disorder often associated with neuroinflammatory processes that contribute to the persistence of recurrent seizures. Conventional antiepileptic drugs (AEDs) frequently fail to achieve complete seizure control, highlighting the urgent need for alternative therapeutic strategies. Recent studies have explored the potential of montelukast, a leukotriene receptor antagonist, in the management of neurological disorders, including epilepsy.

Methods: In the present study, the neuroprotective and antiepileptic effects of montelukast were evaluated using a pentylenetetrazol (PTZ)-induced kindling model in mice. A total of six groups were established, each consisting of nine mice, and animals were randomly assigned to the groups. PTZ (25 mg/kg, i.p.) was administered on alternate days for six weeks to induce kindling. Montelukast (MTK) was tested at three dose levels (5, 10, and 20 mg/kg, i.p.), while levetiracetam (30 mg/kg, i.p.) served as the standard comparator.

Results: Montelukast (20 mg/kg) significantly reduced seizure severity, as indicated by lower Racine scale scores, and improved cognitive performance in both the elevated plus maze and passive avoidance tests. Biochemical analyses demonstrated increased catalase activity, reduced glutamate levels, and elevated γ-aminobutyric acid (GABA) concentrations. Furthermore, montelukast significantly decreased pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as other mediators of neuroinflammation such as high-mobility group box-1 (HMGB1), transforming growth factor-β (TGF-β), matrix metalloproteinase-9 (MMP-9), and toll-like receptor-4 (TLR-4). Histopathological findings confirmed that montelukast administration preserved cortical and hippocampal integrity by reducing neuronal damage.

Conclusion: Collectively, these findings indicate that montelukast exhibits significant anticonvulsant and neuroprotective effects in a PTZ-induced epilepsy model, supporting its potential as a therapeutic candidate for epilepsy and warranting further investigation.

Spinal cord injury (SCI) is a major global health issue with severe complications, yet effective biomarkers remain elusive. We analyzed the GSE226238 dataset from the Gene Expression Omnibus (GEO) database and identified 4621 differentially expressed genes (DEGs) between SCI and controls, comprising 2684 upregulated and 1577 downregulated genes. Functional enrichment analyses revealed these DEGs are predominantly involved in protein degradation pathways, immune-related processes and ubiquitin-mediated proteolysis. Immune infiltration analysis using multiple algorithms showed significant alterations in B cells, T cells, NK cells and neutrophils, indicating a complex immune microenvironment post-SCI. Using WGCNA, we constructed a scale-free co-expression network and identified nine modules; the green module showed the strongest positive correlation with SCI. Intersecting DEGs, WGCNA module genes, and random forest-selected features identified five candidate genes: MAP3K6, ATP5MPL, NDUFB1, RNASE2 and MIR373. Single-cell RNA sequencing further revealed that MAP3K6 exhibited the highest expression among candidates, predominantly in neuroepithelial and neuronal cells. Validation in independent GSE151371 dataset confirmed significantly elevated MAP3K6 expression in SCI, with ROC analysis demonstrating robust diagnostic efficacy (AUC = 0.918). In vitro, MAP3K6 knockdown in mouse spinal cord neuronal cells promoted cell growth and inhibited apoptosis, decreasing pro-apoptotic proteins (BAX, caspase-3, cleaved caspase-3) and increasing anti-apoptotic Bcl-2. Collectively, our multi-omics analysis integrated with experimental validation identifies MAP3K6 as a key regulator in SCI pathogenesis, offering new insights into molecular mechanisms and highlighting its potential as a diagnostic biomarker and therapeutic target.

Background: Existing evidence suggested a relevance between insulin resistance (IR) and stroke, but further confirmation is needed. Research priorities encompass large sample size, stratified analysis, advanced IR index, stroke subtype characterization, and analysis of potential mechanisms.

Methods: We applied multivariable logistic regression using data from National Health and Nutrition Examination Survey 1999-2018 to estimate the correlation between two IR indexes: metabolic score for insulin resistance (METS-IR) and homeostasis model assessment of insulin resistance (HOMA-IR), and stroke. We also performed a two-sample Mendelian randomization (MR) study to detect the causal relationship between IR phenotype, METS-IR, and HOMA-IR as exposures, and stroke as well as its ischemic subtypes as outcomes.

Results: A total of 15,016 participants representing 147,325,838 individuals after weighting were enrolled. Both METS-IR and HOMA-IR were not significantly correlated with stroke after strict adjustment, but METS-IR was strongly related to stroke in individuals aged 20-40 in the stratification analysis. The MR analysis showed robust causal associations between IR phenotype and any stroke (AS) as well as ischemic stroke (IS). Besides AS and IS, METS-IR also had a causal effect on large artery stroke and small vessel stroke.

Conclusion: IR was associated with an increased risk of stroke in young adults.

Aim: To evaluate the efficacy, safety, and dosing of intravenous alteplase administered beyond the conventional 4.5-hour therapeutic window in adults with acute ischemic stroke.

Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Web of Science were searched through December 2025 for randomized controlled trials and observational studies assessing intravenous alteplase administered beyond 4.5 h after stroke onset, including wake-up and imaging-selected strokes. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Outcomes included functional recovery, functional independence, symptomatic intracranial hemorrhage (sICH), and mortality. Sensitivity analyses and Bayesian meta-analyses were also performed.

Results: Ten studies comprising 2,050 patients met the inclusion criteria. Late administration of alteplase was associated with improved functional outcomes, including higher rates of favorable modified Rankin Scale scores (RR 1.34, 95% CI 1.19-1.51) and functional independence (RR 1.17, 95% CI 1.07-1.28). Treatment was associated with an increased risk of sICH (RR 4.67, 95% CI 1.85-11.76), while mortality did not differ significantly between treatment and control groups (RR 1.23, 95% CI 0.87-1.73). Bayesian analysis demonstrated consistent functional benefit with standard-dose alteplase (0.9 mg/kg), whereas reduced-dose regimens did not show consistent efficacy.

Conclusion: Intravenous alteplase administered beyond 4.5 h after stroke onset is associated with improved functional outcomes in selected patients, despite an increased risk of symptomatic intracranial hemorrhage and no significant effect on mortality. These findings support the use of extended-window thrombolysis when guided by appropriate clinical or imaging-based selection criteria.

Introduction: Stroke is a leading cause of mortality and long-term disability in the U.S. and worldwide. Among its key modifiable risk factors, dyslipidemia plays a significant role by accelerating atherosclerosis and impairing cerebrovascular health, thereby substantially increasing stroke incidence.

Methods: We analyzed stroke (ICD-10 codes: I60-I69)-related mortality in patients with dyslipidemia (ICD-10 code: E78), using the CDC-WONDER database from 1999 to 2023. Age-Adjusted Mortality Rates (AAMR) per 100,000 were calculated and categorized by demographics and region. Joinpoint regression was used to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC).

Results: A total of 94,118 stroke-related deaths in individuals with dyslipidemia were recorded aged ≥25 years. The AAMR observed a significantly steep incline from 0.5 in 1999 to 2.97 in 2023 (AAPC: 7.47; 95% CI: 6.54 to 8.40, p < 0.01). Men observed higher overall AAMR (1.64) than women (1.54). Among different races and ethnicities, Non-Hispanic Black population had the highest overall AAMR (1.79). Regionally, the highest overall AAMR was recorded by the West (1.98). Non-metropolitan areas had lower AAMR than metropolitan areas (1.7 vs 1.45).

Conclusion: Stroke-related mortality among individuals with dyslipidemia has risen markedly in the U.S., despite the overall national decline in stroke mortality. This likely reflects the increasing prevalence of metabolic risk factors, an aging population, genetic predisposition, and inadequate lipid management in high-risk groups.