International Journal of Neuroscience最新文献

{"title":"Trans-vatabnet: transcriptomic signatures for Parkinson's disease detection using deep learning.","authors":"Pinki Prakash Vishwakarma, Priya Prakash Vishwakarma, Sucheeth Avanti","doi":"10.1080/00207454.2026.2749803","DOIUrl":"10.1080/00207454.2026.2749803","url":null,"abstract":"<p><p><b>Background:</b> Early detection of Parkinson's disease (PD) is essential for timely clinical intervention. However, transcriptomic-based diagnosis faces challenges associated with high-dimensional gene expression data, redundant features, class imbalance, and limited interpretability.</p><p><p><b>Objective:</b> This study proposes TransVaTabNet, an integrated framework for PD detection and biomarker identification using transcriptomic analysis, deep learning, and explainable artificial intelligence.</p><p><p><b>Methods:</b> RNA-seq data were preprocessed using low-expression gene filtering, Trimmed Mean of M-values (TMM) normalization, and voom transformation. Differentially expressed genes (DEGs) were identified using limma-voom, followed by stage-specific gene analysis and functional enrichment to investigate disease-associated pathways. A Variational Autoencoder (VAE) generated compact latent representations, while the Synthetic Minority Over-sampling Technique (SMOTE) addressed class imbalance. TabNet classified the derived features using sequential attention, and SHapley Additive exPlanations (SHAP) supported model interpretation and potential biomarker identification.</p><p><p><b>Results:</b> Evaluation on the GSE216281 RNA-seq dataset achieved an Area Under the Receiver Operating Characteristic Curve (AUC) of 90.95%, outperforming the classical machine learning models evaluated in this study.Conclusion: TransVaTabNet combines dimensionality reduction, attention-based classification, and explainability to support PD detection and potential biomarker discovery. The framework offers an interpretable approach to identifying disease-associated transcriptomic patterns and may support future precision diagnostic research.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-21"},"PeriodicalIF":1.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking 3D U-Net variants for volumetric segmentation of the substantia nigra and brain ageing related analysis using 7T MRI.","authors":"Ajay Kumar Haridhas, Lenin Fred Alfred","doi":"10.1080/00207454.2026.2749809","DOIUrl":"10.1080/00207454.2026.2749809","url":null,"abstract":"<p><p><b>Objective:</b> Accurate segmentation of the substantia nigra (SN) is essential for assessing its structural integrity and volumetric changes in Parkinson's disease and brain aging. However, it remains challenging due to SN's small size, deep location, and low contrast on conventional MRI. This study benchmarked six U-Net variants baseline 3D U-Net, ResU-Net, SE-U-Net, Attention U-Net, U-Net++, and U-Net 3+ for SN segmentation using ultra-high-field 7 T MRI.</p><p><strong>Methods: </strong>T1-weighted MP2RAGE images from the ATAG dataset (53 healthy subjects: 31 train, 7 validation and 15 test). Six architectures were evaluated: 3D U-Net, ResU-Net, SE-U-Net, Attention U-Net, U-Net++, and U-Net 3+.Performance was evalauted with Dice score, IoU, 95% HD95, ASSD, and also age-stratified analysis was considered for analysing the robustness of model across young, middle-aged, and elderly cohorts.</p><p><strong>Results: </strong>While ResU-Net achieved the highest overlap metrics (Dice = 0.763, IoU = 0.618), where the baseline 3D U-Net outperformed all variants in boundary accuracy (HD95 = 13.85 mm, ASSD = 20.15 mm). The U-Net 3+ and SE-U-Net complex models relatively underperformed, indicated that architectural complexity does not enhance the segmentation performance of small subcortical structures. Descriptive Age-stratified analysis shows, ResU-Net maintained consistent performance across different age groups and 3D U-Net revealed strong age-invariance, however no statistically significant age-group differences were exhibited.</p><p><strong>Conclusions: </strong>This study findings demonstrates architecture selection influences overlap, boundary detection and volume estimation small-structure segmentation and highlights the importance of evaluating model robustness to demographic variability. The findings offer a methodological benchmark for developing reliable SN volumetry tools for neurodegenerative research.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal based Brain Tumor Classification using Clustered Federated Learning in Edge based IoT Network.","authors":"Rohini C, Murugeshwari B","doi":"10.1080/00207454.2026.2749808","DOIUrl":"https://doi.org/10.1080/00207454.2026.2749808","url":null,"abstract":"<p><p>A brain tumor is characterized by the uncontrolled growth of cells that causes a severe impact on the quality of life. Nowadays, various methods based on multimodal medical images are used to identify brain tumors. Meanwhile, these methods require extensive amounts of labeled information to identify disease tissues and often encounter various challenges based on privacy and accuracy. This paper establishes a Taylor-based Focal Log-cosh Entropy Network (TFLE-Net) to classify brain tumors from demographic data and Magnetic Resonance Imaging (MRI) images by utilizing clustered federated learning in an edge-based Internet of Things (IoT) network. The detection process is executed in clustered federated learning concerning two entities: server and nodes. In a local training model, an input MRI scan is pre-processed, further brain tumor areas are segmented, and then, the mining of various features is performed. Simultaneously, the normalization of input demographic data is done, and the suitable features are selected using information gain. Further, the extracted features and chosen features are subjected to TFLE-Net to classify brain tumors. Additionally, the TFLE-Net yielded Mean Absolute Error (MAE) of 0.057, Root Mean Square Error (RMSE) of 0.047, True Positive Rate (TPR) of 97.789%, and accuracy of 96.987%.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-62"},"PeriodicalIF":1.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum CitH3 and PTX3 Levels for Early Prediction of Acute Respiratory Distress Syndrome Following Severe Traumatic Brain Injury.","authors":"Yuming Wang, Ming Lang, Chaojian Zhen, Binchao Liu, Zhiyin Pang, Ying Yang","doi":"10.1080/00207454.2026.2749801","DOIUrl":"https://doi.org/10.1080/00207454.2026.2749801","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the predictive value of serum citrullinated histone H3 (CitH3) and pentraxin 3 (PTX3) for acute respiratory distress syndrome (ARDS) after severe traumatic brain injury (sTBI).</p><p><strong>Methods: </strong>This prospective observational study enrolled 395 consecutive sTBI patients admitted between April 2025 and February 2026. Patients were categorized into ARDS (n = 111) and non-ARDS (n = 284) groups. Serum CitH3 and PTX3 were measured by ELISA. Candidate predictors were selected by LASSO regression. Spearman correlation, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed. The DeLong test, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI) assessed incremental predictive value over the conventional model.</p><p><strong>Results: </strong>Serum CitH3 and PTX3 were significantly higher in the ARDS group (both P < 0.001) and were positively correlated with each other but negatively with oxygenation indices and albumin. Multivariable analysis identified pulmonary contusion, shock, fluid balance within 12 h of admission, APACHE II and SOFA scores, and elevated CitH3 and PTX3 as independent risk factors (all P < 0.05), whereas a higher GCS score and elevated albumin were protective. Their combination yielded an AUC of 0.841, superior to either alone. When added to the conventional model, biomarkers increased the AUC from 0.926 to 0.943 (P = 0.025), with category-free NRI of 0.554 (95% CI: 0.320-0.778, P < 0.001) and IDI of 0.072 (95% CI: 0.040-0.105, P < 0.001).</p><p><strong>Conclusion: </strong>Combined serum CitH3 and PTX3 demonstrate early predictive potential for ARDS after sTBI but require external validation.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myrtenol mitigates seizure activity and oxidative imbalance in a mouse model of PTZ-induced seizure.","authors":"Fatemeh Rasouli, Seyed Hesam Hojjat, Farzaneh Shakeri","doi":"10.1080/00207454.2026.2749811","DOIUrl":"https://doi.org/10.1080/00207454.2026.2749811","url":null,"abstract":"<p><p>Pentylenetetrazole (PTZ)-induced seizures are strongly associated with oxidative imbalance, and the monoterpenoid alcohol myrtenol has been proposed to exert antioxidant and neuroprotective effects. This study investigated whether myrtenol attenuates PTZ-evoked seizure activity and oxidative disturbances in the mouse hippocampus and cerebral cortex. Sixty male mice were assigned to six groups: control, PTZ-only, three myrtenol pretreatment doses (25, 50, 100 mg/kg), and diazepam. Seizure susceptibility was evaluated by measuring latencies to minimal clonic and generalized tonic-clonic seizures following PTZ administration. Oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and total thiol content, were quantified in brain homogenates. PTZ reliably induced seizures and oxidative alterations. Myrtenol pretreatment increased seizure latencies in a dose-dependent manner, although diazepam produced the greatest protection. Myrtenol, particularly at 100 mg/kg, reduced PTZ-induced elevations in MDA and NO, restored SOD and CAT activities, and improved thiol levels, with effects approaching those of diazepam. Lower myrtenol doses produced partial or nonsignificant biochemical improvements. These findings indicate that myrtenol mitigates PTZ-induced seizure expression and oxidative stress, with the highest dose demonstrating the most consistent neuroprotective profile.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-17"},"PeriodicalIF":1.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medial temporal atrophy and posterior cingulate structural covariance in mild cognitive impairment.","authors":"Xiaoming Yang, Jian Lyu, Jubo Wang, Yu Quan","doi":"10.1080/00207454.2026.2733276","DOIUrl":"10.1080/00207454.2026.2733276","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) is associated with structural abnormalities in regions vulnerable to Alzheimer's disease, but the relative contributions of medial temporal, posterior midline, and association cortices remain unclear. We compared regional gray matter volumes between individuals with MCI and cognitively normal (CN) participants and examined their associations with clinical measures, structural covariance, and apolipoprotein E ε4 (APOE ε4) status.</p><p><strong>Methods: </strong>We analyzed 264 participants from the Alzheimer's Disease Neuroimaging Initiative. Gray matter volumes were extracted from seven predefined regions of interest. Group differences and clinical associations were assessed using multivariable regression models adjusted for age, sex, education, and total intracranial volume. Structural covariance analyses examined interregional relationships. Exploratory analyses evaluated ROI-by-APOE ε4 interactions, and sensitivity analyses assessed robustness.</p><p><strong>Results: </strong>Individuals with MCI had smaller hippocampal volumes than CN participants, whereas parahippocampal reductions were less consistent. Smaller hippocampal volume was consistently associated with greater cognitive impairment and poorer functional performance; associations involving the parahippocampal gyrus weakened after adjustment for hippocampal volume. The posterior cingulate cortex showed limited evidence of local volumetric differences but more prominent alterations in structural covariance with medial temporal and temporal association regions. Exploratory APOE ε4 interactions were nominally suggestive but did not survive multiple-comparison correction. Main findings were generally robust across sensitivity analyses.</p><p><strong>Conclusions: </strong>Hippocampal volume showed the most consistent local volumetric and clinical associations in MCI, whereas posterior cingulate abnormalities were more evident in structural covariance patterns. Regional atrophy and altered interregional structural covariance may provide complementary information about brain structural changes in MCI.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":1.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic evidence supports the prioritization of CD40 among prespecified immune-related candidate drug targets in myasthenia gravis.","authors":"Yue Xu, Xiaolei Li, Guangxian Nan","doi":"10.1080/00207454.2026.2733265","DOIUrl":"10.1080/00207454.2026.2733265","url":null,"abstract":"<p><strong>Aim: </strong>To prioritize prespecified immune-related candidate drug targets in myasthenia gravis for further validation based on integrated genetic evidence.</p><p><strong>Methods: </strong>We integrated drug-target Mendelian randomization (MR) using cis-expression quantitative trait loci (cis-eQTLs), protein-level MR of plasma CD40 abundance using plasma protein quantitative trait loci (pQTLs), and colocalization analyses to evaluate genetically proxied associations with overall MG, early-onset myasthenia gravis (EOMG), and late-onset myasthenia gravis (LOMG).</p><p><strong>Results: </strong>In this study, CD40 showed the most consistent genetic evidence among the six prespecified targets. Effect estimates are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Higher CD40 expression proxied by cis-eQTLs was associated with increased risk of overall MG (OR = 1.14, 95% CI: 1.05-1.24, Bonferroni-adjusted <i>p</i> = 0.022) and EOMG (OR = 1.32, 95% CI: 1.12-1.56, Bonferroni-adjusted <i>p</i> = 0.015). Genetically predicted higher plasma CD40 protein abundance was associated with increased overall MG risk (OR = 1.31, 95% CI: 1.08-1.57, Bonferroni-adjusted <i>p</i> = 0.010), whereas the protein-level MR result for EOMG was directionally consistent but not statistically significant. Colocalization analysis provided suggestive but not definitive evidence of colocalization between CD40 expression and EOMG risk. FCGRT, IL2RA, and SYK showed additional exploratory MR signals requiring further validation.</p><p><strong>Conclusion: </strong>CD40 showed the most consistent genetic support among the prespecified targets, supporting its prioritization for functional validation and further therapeutic investigation in MG.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1436-1447"},"PeriodicalIF":1.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin-4 mediated glymphatic dysfunction and neuroinflammatory signaling in neurodegenerative disorders.","authors":"Balbir Singh, Shareen Singh, Souvik Banerjee, Shrey Bhargava, Vetriselvan Subramaniyan, Thakur Gurjeet Singh","doi":"10.1080/00207454.2026.2719591","DOIUrl":"10.1080/00207454.2026.2719591","url":null,"abstract":"<p><p>Aquaporin channels are the predominant fluid regulating channel found in the central nervous system (CNS) and plays a pivotal role in maintaining fluid and ion homeostasis, as well as regulating neuroinflammation, neurodegeneration, and blood-brain barrier (BBB) disruption. This protein is primarily located at astrocytes endfeet within the blood cerebral barrier and other central nervous system (CNS) junctions, facilitating the movement of water in both directions, buffering potassium levels, and aiding in the clearance of interstitial solutes, along with toxic metabolites such as amyloid-β, <i>via</i> the glymphatic system. Changes in the expression or polarization of AQPs are implicated in neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, and ischemic stroke. Impaired functionality of AQPs is involved in a number of pathological processes including heightened oxidative stress, disruption of the blood-brain barrier, and neuroinflammation. Such pathways are targeted by transcription factors, including nuclear factor κB (NFκB), and signaling pathways, including p38 MAPK, that increase AQPs expression following the action of stressors. Furthermore, impairment of AQPs polarity suppresses glymphatic clearance and promotes toxic protein accumulation, one of the key features of Alzheimer 's disease. AQPs structural features, including its six transmembrane helices and conserved NPA motifs, are critical for function, positioning it as a putative therapeutic target. Preclinical data support the notion that modulation of AQPs activity may offer neuroprotection through restoration of homeostasis and reduction of inflammation in neurodegenerative disease. This review describes the mechanistic links between AQPs dysfunction and neurodegenerative disease, highlighting its potential and limitations as a therapeutic target for the prevention of CNS disorders.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1448-1467"},"PeriodicalIF":1.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural exposome burden stratifies cognitive trajectories in a subacute-to-chronic mild TBI outpatient cohort: an exploratory dimension-reduction study.","authors":"Maria T Paulino, Kotaro Tsutsumi, Amanda S Fang, Stephania Tovar Vargas, Maral Sakayan, Seyed Ahmad Sajjadi, Sanaz Attaripour, Michael Lopez, Jeffry Nahmias, Danh V Nguyen, Mark Mapstone, Scott M Bartell, Bernadette Boden-Albala, Patrick M Chen","doi":"10.1080/00207454.2026.2728613","DOIUrl":"10.1080/00207454.2026.2728613","url":null,"abstract":"<p><strong>Aim: </strong>To translate the National Institute of Neurological Disorders and Stroke (NINDS) neural exposome framework into a clinically measurable model for 6-month cognitive trajectory after mild traumatic brain injury (mTBI) using principal component analysis (PCA).</p><p><strong>Methods: </strong>Forty-four adults with mTBI (GCS 13-15; 50% female) were prospectively enrolled at an academic TBI clinic. Fifteen a priori variables spanning Exogenous, Endogenous, and Behavioral exposure categories were assessed. First, an outcome-informed forward-selection procedure identified a coherent 13-variable exposome set, summarized using PCA to derive a cumulative exposome burden score. Cognitive outcome was defined by residualized 6-month Montreal Cognitive Assessment (MoCA) performance dichotomized into worse-than-expected (WTE; ≤ -1 point) and not-worse-than-expected (nWTE) recovery groups. Second, separate PCA analyses were performed within each exposure category, without reference to cognitive outcome, to evaluate internal coherence and directional associations with cognitive recovery.</p><p><strong>Results: </strong>Cross-category PCA identified a latent exposome axis explaining 16.0% of overall variance, driven primarily by education, area deprivation, insurance coverage, PM2.5 exposure, and adverse childhood events. Cumulative exposome burden scores were significantly higher in the WTE group (<i>n</i> = 15) versus nWTE (<i>n</i> = 29) (median PC1: 1.34 vs -0.76; <i>p</i> = 0.010), with similar findings on permutation testing (<i>p</i> = 0.037). Category-level PCA demonstrated coherent internal structure, with first principal components explaining 30.1% (Exogenous), 34.7% (Endogenous), and 39.7% (Behavioral) of within-category variance. Associations with residualized 6-month MoCA were directionally negative across all three categories.</p><p><strong>Conclusions: </strong>Neural exposome burden composites stratified 6-month cognitive trajectories after mTBI. Coherent PCA structure across NINDS-informed exposure categories supports the feasibility of exposome-informed approaches for post-mTBI cognitive risk stratification.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1424-1435"},"PeriodicalIF":1.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-4508 targets PLCB2 in propofol-induced neurotoxicity in sH-SY5Y cells: role and mechanism.","authors":"Zhenbin Zhan, Hai Chen, Jinguang Chen","doi":"10.1080/00207454.2026.2713481","DOIUrl":"10.1080/00207454.2026.2713481","url":null,"abstract":"<p><strong>Objective: </strong>Propofol is a widely administered anesthetic agent given intravenously. This study investigated the function of miR-4508 within propofol-elicited neurotoxicity in SH-SY5Y cells, identified its downstream target genes, and elucidated the underlying molecular regulatory pathway.</p><p><strong>Methods: </strong>Propofol neurotoxicity was modeled in SH-SY5Y cells with varying concentrations and durations. Cell viability, miR-4508, oxidative stress, and inflammatory cytokines were measured. Target prediction and dual-luciferase validation, along with miRNA inhibitor and rescue experiments, were used to elucidate the regulatory mechanism. Cognitive function and hippocampal miR-4508 expression were also preliminarily assessed in propofol-exposed mice using the Morris water maze and RT-qPCR, respectively.</p><p><strong>Results: </strong>Propofol reduced SH-SY5Y cell viability and upregulated miR-4508 in a manner dependent on both concentration and time, peaking at 50 μM for 24 h. Five candidate targets were identified bioinformatically. PLCB2 was most downregulated by miR-4508 overexpression. A dual-luciferase assay verified that miR-4508 directly binds to the PLCB2 3'-UTR. A miR-4508 inhibitor attenuated propofol-induced oxidative stress and inflammation, effects reversed by PLCB2 knockdown. Preliminary <i>in vivo</i> observations suggested impaired learning/memory and increased hippocampal miR-4508 in propofol-treated mice, with miR-4508 inhibition showing a tendency toward reversal of these deficits, though further validation is required.</p><p><strong>Conclusions: </strong>This study demonstrates that propofol upregulates miR-4508 to suppress PLCB2, driving oxidative stress and neuroinflammation. Forward and reverse rescue experiments confirm the miR-4508/PLCB2 axis as a potential therapeutic target for propofol-induced neurotoxicity.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1413-1423"},"PeriodicalIF":1.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}