CNS Neuroscience & Therapeutics最新文献

{"title":"The Plasma Proteome Mediates the Association Between Workplace Noise Exposure and Psychiatric Disorder Risk","authors":"Xuan Zhao,&nbsp;Yan Fu,&nbsp;Dan-Dan Zhang,&nbsp;Wei Xu,&nbsp;Hui-Fu Wang,&nbsp;Wei Zhang,&nbsp;Jin-Tai Yu,&nbsp;Lan Tan","doi":"10.1002/cns.71236","DOIUrl":"https://doi.org/10.1002/cns.71236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Workplace noise exposure has been linked to adverse mental health outcomes, yet the underlying biological processes remain incompletely understood. We aimed to characterize workplace noise-related plasma proteomic profiles, examine the mediating role of circulating proteins in the associations between workplace noise exposure and psychiatric disorders, and quantify individual susceptibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using UK Biobank data, we characterized workplace noise-related proteomic profiles and examined the associations between workplace noise exposure and incident psychiatric disorders. Proteins associated with both exposure and disease risk were identified, followed by functional enrichment and mediation analyses. Workplace Noise-related Protein Risk Scores (WNPRSs) were constructed from shared mediator proteins to assess individual susceptibility, joint risk patterns, and predictive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 229 workplace noise-associated plasma proteins, with assay-specific enrichment predominantly involving extracellular and membrane-associated cellular components. Circulating proteins partially mediated the associations of workplace noise exposure with anxiety disorder and major depressive disorder (MDD), with mediation proportions ranging from 1.9% to 9.2% and 2.5% to 19.4%, respectively. WNPRS-Anxiety and WNPRS-MDD, both based on 44 shared mediator proteins, were associated with workplace noise exposure and the risks of the corresponding psychiatric disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identifies workplace noise-related plasma proteomic signatures, suggests that circulating proteins partly mediate noise-associated psychiatric risk, and highlights the potential utility of WNPRS for characterizing individual susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149356180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-Adrenergic Inhibition Alleviates Post-Hemorrhagic Hydrocephalus by Attenuating Neutrophil Extracellular Traps-Mediated Glymphatic Dysfunction","authors":"Yijian Yang,&nbsp;Yanjie Zhou,&nbsp;Qian Ouyang,&nbsp;Hanati Nuerlanbieke,&nbsp;Yexin Yuan,&nbsp;Junqiang Wang,&nbsp;Kaiyue Wang,&nbsp;Peng Long,&nbsp;Yifeng Chen,&nbsp;Zhikun Liu,&nbsp;Jun Huang,&nbsp;Zhiping Zhang,&nbsp;Zhangjie Su,&nbsp;Xia Wang,&nbsp;Gelei Xiao","doi":"10.1002/cns.71259","DOIUrl":"https://doi.org/10.1002/cns.71259","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Post-hemorrhagic hydrocephalus (PHH) is a devastating complication. This study aims to elucidate how the acute post-hemorrhagic adrenergic storm drives neutrophil extracellular traps (NETs) formation, blocks the glymphatic system (GS), and causes an imbalance in intracranial fluid homeostasis, leading to PHH. It is necessary to explore whether pan-adrenergic inhibition as non-surgical intervention strategies can rescue this neuro-immune dysregulation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Single-cell RNA sequencing (scRNA-seq) was used to draw the immune infiltration map. Utilizing a rat PHH model, ventricular volumes and glymphatic fluid dynamics were assessed via MRI and fluorescent tracer tracking. Multiple behavioral analyses were used to observe the neurological dysfunction. The structural integrity of the GS was assessed using IF staining and TEM. The formation of NETs was detected using ELISA, WB, and IF. In vitro, flow cytometry and molecular assays were used to explore the changes in molecular pathways in epinephrine-stimulated primary neutrophils, and NETs were used to treat astrocytes to study the interaction between them. A pharmacological intervention using pan-adrenergic inhibitor cocktail PPA (prazosin, propranolol, atipamezole), NETs agonist, NETs inhibitor, and AKT activator was conducted to explore the mechanism.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;scRNA-seq identified a pathogenic neutrophil subset presented as a transcriptional phenotype consistent with NETs, which dominated hemorrhagic stroke. Structurally, adrenergic storm-driven NETs extrusion occluded perivascular spaces and stripped aquaporin-4 (AQP4) polarization at astrocytic endfeet, precipitating glymphatic stasis and severe ventricular dilation. Molecular analysis revealed that epinephrine might promote the formation of NETs by activating the PI3K/AKT/mTOR cascade. PPA blocked this pathological axis, inhibited NETs, polarized AQP4 distribution, restored the fluid dynamics of the GS, and relieved cognitive deficits after intraventricular hemorrhage and alleviated hydrocephalus.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;After PHH, targeted pan-adrenergic inhibition can block the adrenergic storm and inhibit NET formation, protect the clearance function and structural integrity of the GS, stabilize the intracranial fluid homeostasis, and alleviate hydrocephalus in the acute phase. The molecular mechanism may involve the PI3K/AKT/mTOR cascade. This mechanism provides a potential therapeutic strategy for neuro-immun","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149356476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Mechanical Perturbation to Pathological Locking: Temporal–Mechanical Evolution of the Postsynaptic Density After Traumatic Brain Injury","authors":"Yibin Jia,&nbsp;Zixuan Cao,&nbsp;Hanjiang Xue,&nbsp;Zhebin Feng,&nbsp;Zhiguo Ma,&nbsp;Zhicheng Tian,&nbsp;Xin Li,&nbsp;Peng Luo","doi":"10.1002/cns.71260","DOIUrl":"10.1002/cns.71260","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) induces persistent cognitive deficits, yet conventional biochemical and structural models often fail to explain synaptic signal collapse in the absence of overt tissue rupture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we present a hypothesis-generating mechanobiological framework that positions postsynaptic density (PSD)—a multivalent protein condensate governed by liquid–liquid phase separation (LLPS)—as a primary locus of synaptic mechanovulnerability. We argue that TBI-induced synaptic pathology is not merely a quantitative loss of molecular components, but a progressive, staged material state transition of the PSD network. This pathological evolution initiates with hyperacute mechanical deconstruction, leading to physical scaffold decoupling and nanoscale receptor misalignment. It then advances through an acute mechano-metabolic crisis characterized by enzymatic scaffold cleavage and impaired re-condensation, ultimately culminating in a chronically locked, low-dynamic “solidified” state. Furthermore, post-injury extracellular matrix stiffening and the mechanical exposure of cryptic epitopes trigger aberrant microglial pruning via mechanosensors such as Piezo1, permanently dismantling neural circuits. Because the supporting evidence is heterogeneous, we explicitly grade each element of this model as established directly in TBI, supported in non-TBI synaptic systems, extrapolated from reconstituted condensates, or hypothetical.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By bridging macroscopic biomechanics with nanoscale molecular pathology, this review highlights a critical conceptual gap and proposes “mechano-therapeutics” as a hypothesis-generating concept rather than an established treatment avenue. We suggest that strategies targeting the physical properties of the synapse, such as stabilizing scaffold oligomerization, modulating mechanotransduction pathways, and restoring physiological tissue stiffness, are candidate directions whose feasibility, delivery, cell-type specificity, timing, and safety must first be established in preclinical models before any clinical translation to rescue synaptic homeostasis and cognitive function after TBI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton Pump Inhibitor Use and Incident Epilepsy in the UK Biobank: Evidence From Pharmacovigilance and Multi-Omics Analyses","authors":"Minghao Li,&nbsp;Yiqian Li,&nbsp;Yuxi Zhang,&nbsp;Balkissou Seebo Saibou,&nbsp;Yifei Chen,&nbsp;Jiayi Xing,&nbsp;Chao Jin,&nbsp;Yuchen Xu,&nbsp;Jiahe Lin,&nbsp;Xinshi Wang","doi":"10.1002/cns.71223","DOIUrl":"10.1002/cns.71223","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Proton pump inhibitors (PPIs) are widely used, but their association with incident epilepsy remains uncertain. We examined this association in the UK Biobank and integrated evidence from pharmacovigilance and multi-omics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 492,858 UK Biobank participants without epilepsy at baseline. Cox models, age- and sex-stratified analyses, active-comparator analyses against H2RA users, propensity score matching, competing-risk models, and sensitivity analyses were performed. FAERS disproportionality, Olink proteomics, and NMR metabolomics provided supportive evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline PPI use was associated with incident epilepsy after full adjustment (HR 1.43, 95% CI 1.29–1.59) and in the PPI-H2RA propensity score-matched analysis (HR 1.41, 95% CI 1.03–1.94). In the GP-linked subset, requiring an ASM prescription within 365 days after diagnosis yielded HR 1.47 (95% CI 1.07–2.02). FAERS showed a PPI-epilepsy reporting signal (ROR 1.70, 95% CI 1.61–1.79). Proteomic and metabolomic analyses identified immune-inflammatory and metabolic associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Baseline PPI use was associated with incident epilepsy in the UK Biobank. Active-comparator, outcome-definition, and prescription-supported analyses supported the primary association. Pharmacovigilance and molecular findings provided complementary evidence but did not establish causality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13732812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrathecal Transplantation of Human Umbilical Cord-Derived MSCs Outperforms Intravenous Administration in Attenuating Pathology and Cognitive Deficits in Alzheimer's Disease Mice","authors":"Li Ding,&nbsp;Wei Yu,&nbsp;Yuqian Chen,&nbsp;Hu Wang,&nbsp;Shuya Li,&nbsp;Hanyu Li,&nbsp;Tianyu Shu,&nbsp;Xiaohe Huang,&nbsp;Ying Yang,&nbsp;Rui Liu,&nbsp;Xinglin Liu,&nbsp;Zhibing Ai,&nbsp;Xingrong Guo,&nbsp;Jun Chen,&nbsp;Qiumin Qu","doi":"10.1002/cns.71215","DOIUrl":"10.1002/cns.71215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mesenchymal stem cell (MSC)-based therapies have emerged as a promising approach for Alzheimer's disease (AD), owing to their neuroprotective, anti-inflammatory, and immunomodulatory properties. However, the optimal delivery route for maximizing therapeutic efficacy within the central nervous system remains unclear. This study aimed to directly compare the therapeutic effects of intravenous versus intrathecal transplantation of human umbilical cord-derived mesenchymal stem cells (HUCMSCs) in a transgenic AD mouse model (5xFAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HUCMSCs were isolated, characterized, and administered to 5xFAD mice via intravenous or intrathecal routes. Cognitive function was assessed using the Morris water maze. Amyloid plaque burden, microglial activation, microglial barrier integrity, and axonal dystrophy were evaluated through immunofluorescence and confocal microscopy. The expression of TREM2, DAP12, and Syk was analyzed to elucidate underlying molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intrathecal transplantation of HUCMSCs significantly improved spatial learning and memory in 5xFAD mice compared to intravenous delivery. HUCMSC treatment substantially reduced amyloid plaque burden and axonal dystrophy, while promoting microglial activation and enhancing the protective function of the microglial barrier. Additionally, HUCMSC administration upregulated TREM2, DAP12, and Syk expression, with intrathecal delivery inducing more robust activation of these microglial signaling pathways than intravenous infusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HUCMSC transplantation alleviates cognitive deficits and modulates key pathological and molecular features of AD in the 5xFAD mouse model, with intrathecal administration demonstrating superior therapeutic efficacy compared to intravenous delivery. These findings underscore the critical importance of optimizing cell delivery routes to enhance the clinical potential of stem cell-based interventions for AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Multidimensional Molecular Mechanisms of Epilepsy and Precision Therapy Strategies","authors":"Yimin Han,&nbsp;Jingxuan Xu,&nbsp;Yuntian Shen,&nbsp;Jitai Zhang,&nbsp;Xia Li,&nbsp;Xinlei Yao,&nbsp;Lei Qi,&nbsp;Hualin Sun","doi":"10.1002/cns.71224","DOIUrl":"10.1002/cns.71224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Epilepsy is a complex neurological disorder characterized by recurrent seizures. A substantial proportion of patients develop drug-resistant epilepsy (DRE), highlighting the limitations of current therapies and the need to view epilepsy beyond the traditional “channelopathy” hypothesis as a multifactorial network disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This narrative review synthesizes current evidence on epilepsy pathogenesis, mechanisms of drug resistance, and emerging therapeutic strategies. Relevant studies were identified through literature searches of PubMed and Web of Science, with emphasis on publications from 2018 to 2025 and landmark studies that have shaped current understanding of epileptogenesis, drug-resistant epilepsy, and precision therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pathogenesis of epilepsy converges genetic, neuroinflammatory, and cellular homeostasis pathways. Key drivers include ion channel mutations, glia-mediated neuroinflammation, and dysregulated processes like autophagy and ferroptosis. These contribute to drug resistance and comorbidities, driving a therapeutic shift toward precision and network-modulation strategies, such as gene therapy, targeted pathway modulation, and neuromodulation, with the ultimate goal of achieving disease modification rather than seizure suppression alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Integrating multi-omics insights to construct a holistic precision medicine framework, spanning from molecular diagnosis to tailored network therapy, is fundamental for advancing epilepsy treatment. Future efforts must focus on translating this integrated understanding into effective clinical strategies to overcome therapeutic resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13733494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Multi-Omics Analysis of Human Cerebrospinal Fluid in Traumatic Spinal Cord Injury: An Exploratory Pilot Study","authors":"Wenkang Jiang,&nbsp;Yao Wang,&nbsp;Wei Miao,&nbsp;Huandong Liu,&nbsp;Qiujiang Qiao,&nbsp;Ting Jiang,&nbsp;Chenyan Shen,&nbsp;Zetian Zhou,&nbsp;Huilin Cheng,&nbsp;Ning Li","doi":"10.1002/cns.71242","DOIUrl":"https://doi.org/10.1002/cns.71242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Acute traumatic spinal cord injury (TSCI) is a devastating neurological disorder with limited therapeutic options. We aimed to characterize the human cerebrospinal fluid (CSF) microenvironment to identify novel multi-omics signatures and potential mechanistic hypotheses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CSF from 13 acute cervical TSCI patients and 13 controls was prospectively collected. A discovery cohort (<i>n</i> = 10) underwent untargeted proteomics and metabolomics. Following differential and functional enrichment analyses, sequential multi-omics integration was applied to extract cross-omics features. Prioritized candidates were subsequently validated via ELISA and targeted metabolomics in an independent validation cohort (<i>n</i> = 16).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 216 differentially expressed proteins and 26 metabolites, highlighting extensive extracellular matrix remodeling alongside profound purine and amino acid metabolism dysregulation. Integrated analyses converged on downregulated mitochondrial aspartate aminotransferase (GOT2) as a candidate marker. Targeted correlation analysis revealed that GOT2 selectively associated with specific co-mapped metabolites that were concurrently downregulated, notably methionine and 4-acetamidobutanoic acid. The GOT2-associated metabolic signature was experimentally validated in the independent cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This exploratory multi-omics study unveils the acute human TSCI molecular landscape, nominating a novel GOT2-associated metabolic signature that warrants further mechanistic investigation regarding its pathogenic implications and potential therapeutic relevance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149310847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Machine Learning Algorithms for Predicting Postoperative Residual Tumor in Pituitary Neuroendocrine Tumors","authors":"Mingrui Li,&nbsp;Chenyang Zhao,&nbsp;Guodong Tang,&nbsp;Yang Li,&nbsp;Qing Liu","doi":"10.1002/cns.71244","DOIUrl":"https://doi.org/10.1002/cns.71244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To develop and validate an interpretable machine learning (ML) model for predicting radiologically confirmed postoperative residual tumor (RT) in pituitary neuroendocrine tumors (PitNETs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 584 surgically treated patients with PitNETs from a single center, using a random 7:3 training–test split and internal cross-validation. The primary endpoint was radiologically confirmed postoperative RT, assessed using MRI obtained within 48 h after surgery and longitudinal follow-up MRI. Candidate variables were selected using LASSO regression, with nine ML algorithms developed. Discrimination, calibration, clinical utility, interobserver agreement, and SHAP-based interpretability were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Postoperative RT occurred in 72 patients (12.3%). Sensitivity analysis showed high agreement between 48-h MRI and follow-up confirmation (96.4%; Cohen's kappa = 0.837). Interobserver agreement was high for retrosellar invasion (kappa = 0.825), internal carotid artery invasion (kappa = 0.960), and Knosp grade (quadratic weighted kappa = 0.994). Eight predictors were retained: maximum sagittal diameter, maximum coronal diameter, age, Knosp grade, internal carotid artery invasion, sphenoid sinus pneumatization, tumor consistency, and retrosellar invasion. In the internal test set, the random forest model achieved high discrimination (AUC = 0.945; accuracy = 0.938), with performance comparable to LightGBM and XGBoost in DeLong testing. LightGBM had the lowest Brier score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Random forest was selected for the web tool after internal evaluation, with discrimination comparable to LightGBM, XGBoost, and SVM. Its generalizability to other centers and future patient cohorts remains unproven because evaluation used only a single-center random split and internal cross-validation. External and temporal validation with calibration assessment is needed before clinical implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149310845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Drop-Seizure Response Patterns to Cannabidiol According to Genetic Status in Lennox–Gastaut Syndrome","authors":"Ji-Hoon Na,&nbsp;Hee yeon Cho,&nbsp;Hayoon Jeon,&nbsp;Hyunjoo Lee,&nbsp;Young-Mock Lee","doi":"10.1002/cns.71221","DOIUrl":"https://doi.org/10.1002/cns.71221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lennox–Gastaut syndrome (LGS) is a genetically heterogeneous developmental and epileptic encephalopathy in which variability in long-term cannabidiol (CBD) response remains incompletely understood. We evaluated whether long-term drop-seizure response trajectories to CBD differ according to genetic status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-center retrospective longitudinal study analyzed systematically collected clinical follow-up data from 61 patients with LGS treated with pharmaceutical-grade CBD; 46 patients with ≥ 24 months of follow-up were included. Patients were classified as pathogenic/likely pathogenic variant-positive (PV+) or variant-negative (PV–). Drop-seizure reduction trajectories were assessed at 3-month intervals over 24 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Drop-seizure reduction improved rapidly and was sustained over 24 months in both PV+ and PV– groups, with no significant differences between groups at the prespecified comparison time points. Longitudinal response trajectories showed substantial overlap, and sustained response was observed in 76.1% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Long-term drop-seizure response to CBD in LGS was sustained but not stratified by genetic status, supporting a syndrome-level treatment approach irrespective of genetic findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal Cerebral Blood Flow Deficits in Behavioral Variant Frontotemporal Dementia: Associations With Clinical Symptoms, Peripheral Vascular Biomarkers, and Neuroimaging Measures","authors":"Jiahui Hou,&nbsp;Qianqian He,&nbsp;Xiuxia Fu,&nbsp;Yufei Chen,&nbsp;Hua Lu,&nbsp;Yuxuan Xu,&nbsp;Liyong Wu,&nbsp;Min Chu","doi":"10.1002/cns.71235","DOIUrl":"https://doi.org/10.1002/cns.71235","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to characterize regional cerebral blood flow (CBF) alterations in behavioral variant frontotemporal dementia (bvFTD), examine their associations with clinical symptoms and peripheral vascular/synaptic biomarkers, evaluate spatial concordance with gray matter volume (GMV) loss and glucose hypometabolism, and explore CBF's mediating role between biomarkers and clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-five bvFTD patients and 27 matched normal controls (NC) underwent clinical assessments, ASL MRI, ¹⁸F-FDG PET, and structural MRI. Plasma vascular (VEGFA, PDGF-BB) and synaptic (NPTXR, NPTX2) biomarkers were measured via the Olink platform. Statistical analyses included group comparisons, ROC analysis, multiple linear regression, and mediation analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with normal controls, bvFTD patients exhibited significantly reduced CBF in both frontal and temporal regions, which showed regional spatial concordance with GMV and FDG uptake in corresponding areas. Frontal CBF demonstrated good diagnostic accuracy and was significantly associated with multiple clinical measures including MMSE, MoCA, ADL, and behavioral scales, as well as with peripheral vascular and synaptic biomarkers. Exploratory mediation analyses suggested statistical indirect associations linking peripheral vascular biomarkers to clinical symptoms through frontal CBF and linking frontal CBF to behavioral outcomes through frontal GMV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BvFTD is characterized by frontotemporal hypoperfusion, with frontal CBF closely associated with cognitive, behavioral, and functional impairment. The regional concordance of ASL-derived CBF with gray matter atrophy and glucose hypometabolism supports its potential role as an accessible, non-invasive, and radiation-free complementary neuroimaging biomarker. The mediation findings should be considered hypothesis-generating because they did not remain significant after FDR correction and require validation in larger longitudinal studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}