The International Journal Of Neuroscience[JOURNAL]
Sun
200 papers
Purinergic signaling: a novel therapeutic target in depression.
Cui Q, Li Y, Gao S … +2 more , Zhou H, Peng Y
Int J Neurosci · 2026 May · PMID 42060939 · Publisher ↗
Major depressive disorder, as a common neuropsychiatric disorder, has a complex pathogenesis that has not yet been fully elucidated, posing significant challenges to clinical treatment. In recent years, the role of the p...
Major depressive disorder, as a common neuropsychiatric disorder, has a complex pathogenesis that has not yet been fully elucidated, posing significant challenges to clinical treatment. In recent years, the role of the purinergic signaling system in the pathophysiological processes of depression has garnered increasing attention. The purinergic signaling primarily involves extracellular purine compounds such as ATP and adenosine, which act as transmitters by binding to their corresponding purine receptors (P1 and P2). Purinergic signaling can participate in depression by affecting the function of astrocytes, neuronal plasticity, and the activity of microglia. This paper systematically reviews the latest research advancements in purinergic signaling related to depression by searching for articles on the PubMed using the keywords 'purinergic' OR 'ATP' OR 'adenosine' and 'depression'. It focuses on the molecular mechanisms of action and discusses the limitations and controversial issues present in current research, aiming to provide new theoretical foundations and treatment strategies for the precise treatment of depression.
Identification of PANoptosis-related biomarkers in spinal cord injury (SCI) through multi-omics analysis and machine learning.
Xu S, Wang G, Zhang X … +3 more , Dong X, Liang J, Bai T
Int J Neurosci · 2026 Jul · PMID 42037113 · Publisher ↗
BACKGROUND: Spinal cord injury (SCI) is a severe neurological disorder lacking early diagnostic biomarkers and precise therapeutic targets. PANoptosis, a combined cell death process involving apoptosis, necroptosis, and...
BACKGROUND: Spinal cord injury (SCI) is a severe neurological disorder lacking early diagnostic biomarkers and precise therapeutic targets. PANoptosis, a combined cell death process involving apoptosis, necroptosis, and pyroptosis, is implicated in poor functional recovery after SCI, yet its biomarkers remain unexplored. This study aims to identify biomarkers associated with PANoptosis in SCI. METHODS: Differentially expressed genes (DEGs) associated with SCI were identified using bioinformatics analysis, followed by functional enrichment. Weighted gene co-expression network analysis (WGCNA) and three machine learning algorithms (random forest, LASSO, and SVM-RFE) were used to identify core PANoptosis-related genes. A protein-protein interaction network and a nomogram model were constructed, and immune infiltration was analyzed. Gene expression and function were validated using an LPS-induced BV2 microglial injury model. RESULTS: A total of 1,167 DEGs were identified, mainly enriched in immune and calcium signaling pathways. Five core genes (PPP3CC, DFFB, PSMA6, PRKCQ, and PIK3CB) were identified through integrated analysis. The nomogram showed that higher PIK3CB and PSMA6 expression was associated with increased risk, whereas higher PPP3CC, DFFB, and PRKCQ expression indicated lower risk. These genes were significantly correlated with multiple immune cell subsets. experiments confirmed altered protein expression after LPS stimulation, with PPP3CC most notably downregulated. PPP3CC overexpression partially restored cell viability and reduced IL-6, IL-1β, and TNF-α levels. CONCLUSION: PANoptosis appears to play a significant role in the pathogenesis of SCI. The identified genes are potential biomarkers of immune regulation, and PPP3CC may serve as a protective factor and therapeutic target.
The predictive value of serum CXCL2 and CXCL8 levels for early neurological deterioration in patients with penetrating artery disease-type ischaemic stroke.
Zhong Y, Liu B
Int J Neurosci · 2026 Jul · PMID 42035350 · Publisher ↗
OBJECTIVE: To evaluate whether serum C-X-C motif chemokine ligand 2 (CXCL2) and C-X-C motif chemokine ligand 8 (CXCL8) predict early neurological deterioration (END) in penetrating artery disease (PAD)-type ischaemic str...
OBJECTIVE: To evaluate whether serum C-X-C motif chemokine ligand 2 (CXCL2) and C-X-C motif chemokine ligand 8 (CXCL8) predict early neurological deterioration (END) in penetrating artery disease (PAD)-type ischaemic stroke. METHODS: This retrospective study included 146 PAD patients (June 2022-October 2024). Patients were stratified into END ( = 22) and non-END ( = 124) groups. Bioinformatics analysis using the GEO database and protein-protein interaction (PPI) analysis were performed. Serum CXCL2 and CXCL8 levels were measured by enzyme-linked immunosorbent assay (ELISA). Pearson correlation, receiver operating characteristic (ROC) curve, and logistic regression analyses were performed, followed by nomogram construction. RESULTS: Bioinformatics analysis revealed CXCL2 and CXCL8 upregulation in cerebral infarction. END patients were older, had prolonged onset-to-admission times, higher admission National Institutes of Health Stroke Scale scores, and a higher branch atheromatous disease prevalence (all < 0.05). END patients had elevated serum CXCL2 and CXCL8 levels ( < 0.05), which were positively correlated ( = 0.202, = 0.015). ROC analysis indicated that the combination of CXCL2 and CXCL8 produced an area under the curve of 0.799 (95% CI: 0.720-0.878), outperforming individual markers. LASSO regression identified age, CXCL2, and CXCL8 as key variables. Multivariate analysis revealed age (OR = 1.140, 95% CI: 1.053-1.235, = 0.001), CXCL2 (OR = 1.024, 95% CI: 1.006-1.043, = 0.008), and CXCL8 (OR = 1.009, 95% CI: 1.003-1.016, = 0.003) as independent END risk factors. The nomogram demonstrated excellent discrimination (training: 0.874; validation: 0.856) and good calibration (Hosmer-Lemeshow > 0.05). CONCLUSIONS: Serum CXCL2 and CXCL8 demonstrate potential as biomarkers for identifying END in acute PAD.
Clinical association of serum miR-524-5p levels with injury severity and prognostic outcomes in traumatic brain injury.
Yu X, Hu Z
Int J Neurosci · 2026 Jul · PMID 42015739 · Publisher ↗
BACKGROUND: Traumatic Brain Injury (TBI) has a complex pathology, with no specific biomarkers for diagnosis/prognostic stratification. miRNAs are key regulators of TBI pathological progression. OBJECTIVE: To assess miR-5...
BACKGROUND: Traumatic Brain Injury (TBI) has a complex pathology, with no specific biomarkers for diagnosis/prognostic stratification. miRNAs are key regulators of TBI pathological progression. OBJECTIVE: To assess miR-524-5p's diagnostic/prognostic value in TBI and its regulation of BV2 microglia. METHODS: 150 TBI patients (varying severity) and 45 controls were recruited. Serum miR-524-5p was quantified; Receiver operating characteristic (ROC)/proportional hazards model (Cox) analyses linked it to TBI severity and 28-day outcomes. LPS-stimulated BV2 cells were used to test their effects on viability, proliferation, apoptosis, inflammation, and oxidative stress. RESULTS: miR-524-5p was significantly elevated in TBI (positively correlated with severity), with good diagnostic value for TBI subtypes. High expression independently predicted poor TBI outcomes and severe TBI 28-day mortality (all < 0.05). It inhibited BV2 proliferation, promoted apoptosis, and exacerbated LPS-induced inflammation (IL-6, TNF-α, IL-1β) and oxidative stress. CONCLUSION: miR-524-5p is a potential TBI diagnostic/prognostic biomarker, regulating microglia-mediated neuroinflammation and oxidative stress, and offering new insights into TBI pathobiology.
Lumbar spine disorder detection using segmentation and IBN-MGNet classification with enhanced feature extraction.
Surendra K, Reddy BE
Int J Neurosci · 2026 Jul · PMID 42010362 · Publisher ↗
Back pain affects millions worldwide, with lumbar spine disorders (LSDs) being a major contributing factor due to the spine's critical role in supporting body weight. This study aims to improve the detection of LSDs usin...
Back pain affects millions worldwide, with lumbar spine disorders (LSDs) being a major contributing factor due to the spine's critical role in supporting body weight. This study aims to improve the detection of LSDs using advanced deep learning techniques. The proposed framework introduces a novel pipeline that begins with bilateral filtering for image preprocessing, followed by segmentation using a Proposed Residual Block with Patch-based RESU-NET (PRB-PRESU-NET). Feature extraction integrates Gaussian Filter with Scharr Operator-based Gradient Local Ternary Patterns (GSO-GLTP), MT, and deep features, where the Scharr operator enhances edge detection compared to conventional Sobel filters. Finally, classification is performed using the Improved Bottle Neck-based Modified GhostNet (IBN-MGNet), which achieves a high accuracy of 0.9312, outperforming existing methods. The innovation lies in the integration of refined segmentation, feature extraction, and classification strategies, resulting in a reliable and precise system for LSD detection.
Bidirectional Mendelian randomization study of causal associations between white-matter structural connectivity and multiple sclerosis.
Yu Z, Chen H, Zhang Z … +4 more , Xiong Y, Zha J, Deng L, Zhang X
Int J Neurosci · 2026 Jul · PMID 41975653 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) is associated with widespread network disruption, but whether specific white-matter structural connectivity (WMSC) phenotypes contribute causally to MS susceptibility remains unclear....
BACKGROUND: Multiple sclerosis (MS) is associated with widespread network disruption, but whether specific white-matter structural connectivity (WMSC) phenotypes contribute causally to MS susceptibility remains unclear. METHODS: We performed bidirectional two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary statistics for 206 tractography-derived WMSC phenotypes (UK Biobank; = 26,333) and MS susceptibility (IMSGC; = 115,803 of European ancestry). Primary inference used inverse-variance weighted (IVW) MR under a multiplicative random-effects model, complemented by MR-Egger, weighted median, weighted mode, and simple mode. RESULTS: In forward MR, 12 WMSC phenotypes remained associated with MS susceptibility after direction-concordance filtering and robustness assessment. These signals were not randomly distributed across the structural connectome: risk-increasing effects were concentrated in salience/control-related cortico-subcortical and sensorimotor couplings, particularly connections involving the amygdala, putamen, and contralateral somatomotor network, whereas inverse associations were more prominent in default-mode/limbic and cross-network connections, including limbic-accumbens, limbic-caudate, default-mode-hippocampus, and visual-default-mode links. Sensitivity analyses did not indicate directional pleiotropy, outlier-driven distortion, or single-variant dependence among the retained traits. No reverse causal effect of MS liability on the prioritized WMSC phenotypes was supported. CONCLUSIONS: These bidirectional MR results support a circuit-selective model in which genetically influenced variation in specific cortico-subcortical WMSC phenotypes is associated with MS susceptibility, with risk-increasing effects concentrated in salience/control-basal ganglia-sensorimotor circuits and inverse associations enriched in default-mode/limbic and cross-network couplings. The absence of robust reverse effects is more consistent with predisposing connectivity architectures than with MS liability causally altering WMSC.
Methylation of tenascin XB mediated by methyltransferase-like 3 can effectively suppress neural injury and cellular apoptosis induced by ischemic stroke.
Ding L, Feng X, Gao F
Int J Neurosci · 2026 Jul · PMID 41968052 · Publisher ↗
BACKGROUND: Ischemic stroke (IS), a cerebrovascular disorder due to brain vessel blockage, poses a direct life-threatening risk. Tenascin XB (TNXB), a glycoprotein, is key in regulating extracellular matrix structure and...
BACKGROUND: Ischemic stroke (IS), a cerebrovascular disorder due to brain vessel blockage, poses a direct life-threatening risk. Tenascin XB (TNXB), a glycoprotein, is key in regulating extracellular matrix structure and signal transduction. This study aims to unveil the mechanism by which TNXB alleviates IS. METHODS: Differentially expressed genes (DEGs) in IS were screened from GSE58294 dataset, and GO and KEGG enrichment analyses of DEGs were conducted using the SangerBox website. Protein expression was detected by western blot; cell viability was assessed CCK-8 assay; LDH release was measured with an LDH assay kit; and cell apoptosis rate was evaluated by flow cytometry. TNXB mRNA modification sites were predicted using SRAMP website; the N6-methyladenosine (m6A) level of RNA was detected using MeRIP assay; the half-life of TNXB mRNA was assessed by actinomycin D assay. RESULTS: In IS, TNXB was underexpressed and associated with the PI3K-Akt pathway. Overexpression of TNXB reversed the OGD/R-induced decline in SK-N-SH cell viability, the increase in LDH levels, and the exacerbation of apoptosis. Methyltransferase-like 3 (METTL3) stabilized TNXB expression the m6A methylation mechanism. By targeting TNXB, METTL3 mitigated OGD/R-induced cell damage. Additionally, METTL3 activated the PI3K-Akt pathway targeting TNXB. CONCLUSIONS: METTL3 stabilizes TNXB expression through m6A methylation modification, thereby alleviating IS-induced cellular damage. This suggests that targeting the METTL3-TNXB axis may represent a potential therapeutic strategy for IS.
Scalable quantum non-local neural network optimised with the tyrannosaurus algorithm for brain tumour detection using MRI images.
Chidambaram P, Agrawal G, Loganathan G … +1 more , Jaiprakash A
Int J Neurosci · 2026 Jul · PMID 41967037 · Publisher ↗
Early and reliable detection of brain tumours using magnetic resonance imaging (MRI) is essential for timely diagnosis and effective treatment planning. However, automated tumour detection remains challenging due to tumo...
Early and reliable detection of brain tumours using magnetic resonance imaging (MRI) is essential for timely diagnosis and effective treatment planning. However, automated tumour detection remains challenging due to tumour heterogeneity, complex brain anatomy, image noise, and the limited ability of many deep learning models to capture both global and fine-grained features. Existing approaches also often suffer from high computational complexity and limited generalisability across datasets. This study aims to develop an efficient and robust automated framework for accurate brain tumour detection from MRI images while addressing limitations related to feature representation, computational efficiency, and model generalisability. A novel framework integrating advanced preprocessing techniques, accurate tumour segmentation, hierarchical feature extraction, and optimised classification is proposed. The model was evaluated using two publicly available benchmark datasets, BraTS 2018 and Figshare, comprising multi-class brain tumour MRI images with different tumour types and grades. The proposed framework achieved superior performance, with classification accuracy reaching up to 99.8%. Comparative analysis demonstrated improvements in precision, recall, and F1-score over existing state-of-the-art methods. The model also exhibited enhanced feature representation capabilities and reduced computational errors when processing complex tumour structures. The proposed approach provides a reliable and efficient computer-aided diagnostic tool for brain tumour detection. Its high accuracy and robustness across datasets make it a promising tool for assisting clinicians in early diagnosis and informed decision-making, thereby potentially improving clinical outcomes.
Platelet-to-lymphocyte ratio as an inflammatory marker associated with stroke severity in acute ischemic stroke: a prospective observational study.
Janakiraman S, N K, Pravin Coumar C
Int J Neurosci · 2026 Jul · PMID 41919755 · Publisher ↗
Stroke is a major cause of disability and mortality in India, occurring as ischemic or hemorrhagic. Platelets drive thrombosis and inflammation, while lymphocytes exert anti-inflammatory effects. The platelet-to-lymphocy...
Stroke is a major cause of disability and mortality in India, occurring as ischemic or hemorrhagic. Platelets drive thrombosis and inflammation, while lymphocytes exert anti-inflammatory effects. The platelet-to-lymphocyte ratio (PLR) reflects these opposing mechanisms. This study evaluated PLR in acute ischemic stroke and its correlation with 'National Institutes of Health Stroke Scale (NIHSS)'. A prospective observational study was conducted at Sri ManakulaVinayagar Medical College, Puducherry (January-December 2023). Sixty-four acute ischemic stroke patients were evaluated. NIHSS was recorded, and PLR calculated from complete blood counts at admission and after five days. Most patients were above 45 years (87.5%) and male (60.9%). Dyslipidemia (65.6%) and diabetes mellitus (64.1%) were the commonest comorbidities. The middle cerebral artery was most frequently affected (48.4%). PLR showed a significant positive correlation with NIHSS at admission and day five. PLR is a simple, cost-effective marker for predicting stroke severity and outcomes, aiding management decisions.
Therapeutic role of miR-296-5p in hypertensive stroke through ACE2-dependent Edn1 suppression.
Li J, Chen F, Liu C … +1 more , Xu F
Int J Neurosci · 2026 Jul · PMID 41906983 · Publisher ↗
OBJECTIVE: This study investigated the mechanism of miR-296-5p in hypertensive stroke. METHODS: Ten patients with acute stroke and ten healthy volunteers were selected. EPCs were isolated and transfected, followed by ass...
OBJECTIVE: This study investigated the mechanism of miR-296-5p in hypertensive stroke. METHODS: Ten patients with acute stroke and ten healthy volunteers were selected. EPCs were isolated and transfected, followed by assessment of cell activities. A mouse middle cerebral artery occlusion (tMCAO) model was established, and neural function deficits were evaluated using neural function score, forelimb placement test, and balance beam walking test. ACE2 and Mas receptor expression were assessed by TUNEL staining and immunohistochemical analysis. Serum Ang-(1-7) levels were measured using an ELISA kit. miR-296-5p, ACE2, and Mas were detected by RT-qPCR. The binding relationship between miR-296-5p and ACE2 was verified by dual luciferase assay and FISH. RESULTS: miR-296-5p expression was elevated in the peripheral blood of stroke patients. Lower HDL-C levels were associated with higher hemorrhagic volume, increased NIHSS score, and elevated miR-296-5p expression. miR-296-5p expression was also increased in brain tissue of tMCAO mice. Knockdown of miR-296-5p increased neuron numbers, indicating enhanced survival and reduced apoptosis. The decrease in Ang-(1-7) following miR-296-5p knockdown may reflect a feedback mechanism involving ACE2 regulation. Additionally, miR-296-5p targeted ACE2 expression, which may indirectly regulate Mas transcription through signaling pathways involved in neuroinflammation and ischemic injury. Overexpression of ACE2 reduced the effect of miR-296-5p knockdown on neural repair in tMCAO mice. CONCLUSION: Serum miR-296-5p is a highly predictive marker for stroke prognosis. miR-296-5p alleviates hypertensive stroke by inhibiting Edn1 through ACE2.
Self-improved LeNet and modified SegNet for Alzheimer's disease classification using MRI.
R S R, G S G, S S … +2 more , P A, K A
Int J Neurosci · 2026 Jul · PMID 41830915 · Publisher ↗
Alzheimer's disease 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 beli...
Alzheimer's disease 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 Alzheimer's disease is the shrinkage of the hippocampus and frontal lobe cortex. Magnetic resonance imaging is frequently used to diagnose Alzheimer's disease 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 framework. The proposed Multi-head Parallel LeNet5-based Alzheimer's Disease Classification system processes magnetic resonance imaging images through several key steps. First, the Modified Wiener Filter is applied for noise reduction during preprocessing. Next, Pyramid Convolutional Kernels-based SegNet performs segmentation to isolate relevant brain regions. In the feature extraction phase, Improved Local Gabor Binary Pattern Histogram Sequence, 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 Alzheimer's disease. The Multi-head Parallel LeNet5-based Alzheimer's Disease Classification model predicts a higher accuracy score of 98% to confirm that it more consistently classifies Alzheimer's disease using magnetic resonance imaging.
Key challenges in traumatic brain injury treatment: integrated mechanisms, translational animal models, and advanced drug delivery systems.
Yang J, Zhang Y, Wang J … +1 more , Ma S
Int J Neurosci · 2026 Jul · PMID 41830127 · Publisher ↗
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. This review integrate...
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. 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. 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. 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.
Language-related functional connectivity in post-stroke aphasia: preliminary findings from a graph-theoretical and interpretable machine learning study.
Hoang NT, Karmonik C, Walpola T … +3 more , Dilhani N, Masahiro A, Senoo A
Int J Neurosci · 2026 Jul · PMID 41820794 · Publisher ↗
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...
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 ( = 22) and low-level ( = 35) groups using an ability-matched auditory-verbal fMRI paradigm. Functional connectivity was modeled ROI-to-ROI generalized psychophysiological interactions, from which graph metrics for predefined language nodes were extracted. Network measure differences were assessed 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 ( = 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.
Summary of the best evidence for frailty management in patients with ischemic stroke during the rehabilitation period.
Liu S, Wang X, Zhang Z
Int J Neurosci · 2026 Jun · PMID 41818672 · Publisher ↗
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 fo...
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.
Integrating neurotrophic and anti-inflammatory pathways: press-needle acupuncture as a multi-target therapy for adolescent depression.
Zhang H, Rong Y, Ning R … +3 more , Yan Z, Zhao Y, Chen Y
Int J Neurosci · 2026 Jun · PMID 41811179 · Publisher ↗
BACKGROUND: Press needle therapy, may alleviate depressive-like behaviors. METHODS: Male rats were randomly allocated into four groups ( = 8): Normal control group (CON), Chronic Unpredictable Mild Stress(CUMS) group (CU...
BACKGROUND: Press needle therapy, may alleviate depressive-like behaviors. METHODS: Male rats were randomly allocated into four groups ( = 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.
Modulation of the HMGB1/TLR4 pathway by montelukast in PTZ-induced epilepsy: alleviating neuroinflammatory oxidative stress and seizure severity.
Bano A, Nidhi, Samim M … +1 more , Khan MA
Int J Neurosci · 2026 Jun · PMID 41793129 · Publisher ↗
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 ac...
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. : 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. : 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. : 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.
High MAP3K6 expression in spinal cord injury tissues enhances neuronal apoptosis: insights from multi-omics data integrating WGCNA, machine learning and experimental validation.
Liu Y, Liu Z, Shi Y
Int J Neurosci · 2026 Jun · PMID 41782555 · Publisher ↗
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...
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). , 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.
Insulin resistance increases stroke risk: a cross-sectional study from NHANES 1999-2018 and a Mendelian randomization study.
Hu Y, Zou F, Zhou Z … +1 more , Lu W
Int J Neurosci · 2026 Jun · PMID 41779139 · Publisher ↗
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,...
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.
Rising mortality and post-COVID shifts due to stroke in adults with dyslipidemia in the U.S. from 1999 to 2023: analysis of the CDC WONDER database.
Saghir M, Affan M, Ahmed AM … +8 more , Mateen H, Shoaib N, Nabi R, Zafar M, Rawal S, Sattar Y, Ahmed R, Mahmud Nishat S
Int J Neurosci · 2026 Jun · PMID 41773527 · Publisher ↗
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 im...
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, < 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.
Efficacy, safety and dosing of intravenous alteplase administered beyond 4.5 hours for ischemic stroke: systematic review and meta-analysis.
Alrabadi B, Alghzawi Y, Mater HI … +4 more , Bandak N, Alshakshir AE, Saleh R, Alkayed HA
Int J Neurosci · 2026 Jun · PMID 41770526 · Publisher ↗
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-anal...
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.
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