CNS Neuroscience & Therapeutics最新文献

{"title":"Early Prediction of the Evolution of Self-Limited Epilepsy With Centrotemporal Spikes to Epileptic Encephalopathy With Spike-and-Wave Activation in Sleep: A Prediction Model Construction Based on Quantitative Electroencephalography Characteristics","authors":"Zimeng He,&nbsp;Linghui Zhu,&nbsp;Zaifen Gao,&nbsp;Yumei Li,&nbsp;Xiaoyu Zhao,&nbsp;Xiaofan Yang,&nbsp;Lili Tong,&nbsp;Guijuan Jia,&nbsp;Dongqing Zhang,&nbsp;Baomin Li","doi":"10.1111/cns.70268","DOIUrl":"https://doi.org/10.1111/cns.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To predict the progression of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) to epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of early clinical and electroencephalography (EEG) data. Clinical parameters included demographic and epilepsy-related characteristics. EEG were qualitatively (localization, lateralization, synchrony, non-Rolandic discharges, nondipole spikes, multiple spikes, focal slow-wave activity) and quantitatively (spike–wave index [SWI], spike–wave frequency [SWF], power spectral density [PSD], phase-locking value [PLV], phase lag index [PLI], weighted phase lag index [wPLI], characteristic path length [CPL], clustering coefficient [CC], small-worldness [Sigma]) analyzed. A logistic regression-based prediction model was further formulated and evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 50 children with seizure-free typical SeLECTS and 76 who developed EE-SWAS. Multivariable logistic regression revealed that early EEG features—SWF, relative PSD in the alpha band, wPLI and CPL in the delta band—were associated with the risk of encephalopathic transformation. The model demonstrated good performance with an area under the curve of 0.817 (95% confidence interval 0.736–0.898). The model showed a good fit and clinical benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Initial quantitative EEG characteristics of SeLECTS can predict the development of EE-SWAS, suggesting distinct disease characteristics and pathogeneses in children at risk of encephalopathic transformation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638906","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":"Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis","authors":"Zhipeng Jiang,&nbsp;Hanxue Huang,&nbsp;Youwei Guo,&nbsp;Zihan Wang,&nbsp;Hailong Huang,&nbsp;Wen Yin,&nbsp;Haoxuan Huang,&nbsp;Lei Wang,&nbsp;Weidong Liu,&nbsp;Xingjun Jiang,&nbsp;Caiping Ren","doi":"10.1111/cns.70330","DOIUrl":"https://doi.org/10.1111/cns.70330","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, <i>TOM1L1</i> (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as <i>TOM1L1</i>, demonstrated high predictive accuracy (c-index = 0.867)—the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. <i>TOM1L1</i> emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632815","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":"Proteomic Analyses of Clots Identify Stroke Etiologies in Patients Undergoing Endovascular Therapy","authors":"Tae Jung Kim,&nbsp;Jin Woo Jung,&nbsp;Young-Ju Kim,&nbsp;Byung-Woo Yoon,&nbsp;Dohyun Han,&nbsp;Sang-Bae Ko","doi":"10.1111/cns.70340","DOIUrl":"https://doi.org/10.1111/cns.70340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the correlation between clot composition and stroke mechanisms in patients undergoing endovascular therapy (EVT), using proteomic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 35 patients with ischemic stroke (cardioembolism [CE], <i>n</i> = 17; large artery atherosclerosis [LAA], <i>n</i> = 6; cancer-related [CR], <i>n</i> = 4; and undetermined (UD) cause, <i>n</i> = 8) who underwent EVT. Retrieved clots were proteomically analyzed to identify differentially expressed proteins associated with the three stroke mechanisms and to develop the machine learning model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the discover stage, 3838 proteins were identified using clot samples from 27 patients with CE, LAA, and CR mechanisms. Through functional enrichment and network analysis, 149 proteins were identified as potential candidates for verification studies. After verification experiments, 34 proteins were selected as the final candidates to predict stroke mechanisms. Furthermore, the machine learning-based model identified three proteins associated with each mechanism (Pleckstrin in CE; CD59 glycoprotein in LAA; and Immunoglobulin Heavy Constant Gamma 1 in CR) in the UD group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified specific protein markers of clots that could differentiate stroke mechanisms in patients undergoing EVT. Therefore, our results could offer valuable insights into elucidating the mechanisms of ischemic stroke, which could provide information on more effective secondary prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612469","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":"Anwulignan Alleviates Bone Cancer Pain by Modulating the PPARα/CXCR2 Signaling Pathway in the Rat Spinal Cord","authors":"Yueliang Wang,&nbsp;Qingying Liu,&nbsp;Yingying Jiang,&nbsp;Longfei Mao,&nbsp;Mohamed Zoubaa,&nbsp;Jian Wang,&nbsp;Huilian Bu,&nbsp;Minyu Ma,&nbsp;Jingjing Yuan,&nbsp;Jing Cao,&nbsp;Xiaochong Fan","doi":"10.1111/cns.70302","DOIUrl":"https://doi.org/10.1111/cns.70302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Advanced cancer patients frequently endure severe pain from bone metastases, and few effective treatments for bone cancer pain (BCP) exist. Although Anwulignan is known for its antioxidant, anti-inflammatory, and antitumor properties, its effects on BCP remain unclear. This study aims to explore the analgesic effects and mechanisms of Anwulignan on bone cancer pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Western blotting and immunofluorescence assessed molecular expression and localization. X-ray, micro-CT, TRAP, and ALP staining examined bone destruction in rats. MTT, colony formation assays, and in vivo imaging analyzed tumor changes. RNA-Seq identified differentially expressed genes, validated by ChIP analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we showed that Anwulignan alleviated mechanical, thermal, and cold hypersensitivity and spontaneous pain, prevented bone destruction, and suppressed local tumor growth in rats with BCP. Furthermore, Anwulignan was firmly bound to proliferator-activated receptor alpha (PPARα), increasing its thermal stability. Intrathecal (i.t.) injection of PPARα siRNA increased pain sensitivity in naive rats, and PPARα siRNA abrogated the analgesic effect of Anwulignan in BCP model rats. Moreover, the PPARα agonist pirinixic acid reduced BCP hypersensitivity and abrogated the upregulation of CXC chemokine receptor 2 (CXCR2). Importantly, PPARα bound to the CXCR2 promoter region, and Anwulignan could reverse the reduced binding of PPARα to CXCR2 caused by BCP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these results indicate that Anwulignan is a potential antitumor and analgesic agent that exerts its effects via upregulation of PPARα expression to inhibit the expression of CXCR2 and could be used for treating BCP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612414","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":"Association of Early Blood Pressure Levels and Outcomes in Ischemic Stroke Treated With Intravenous Thrombolysis: A Prospective Cohort Study","authors":"Luyi Zhu,&nbsp;Jiali Xie,&nbsp;Qingjian Xie,&nbsp;Yiting Xu,&nbsp;Yinuo Chen,&nbsp;Yaojia Li,&nbsp;Junwei Zhang,&nbsp;Chunyang Pang,&nbsp;Lingfei Gao,&nbsp;Huan Yu,&nbsp;Binbin Deng","doi":"10.1111/cns.70318","DOIUrl":"https://doi.org/10.1111/cns.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Current guidelines for acute ischemic stroke (AIS) treatment recommend a lenient upper blood pressure (BP) threshold of 185/110 mmHg. However, stricter BP control has been reported to improve prognosis. This study aims to identify the optimal BP range following thrombolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational study included 340 AIS patients treated with rt-PA thrombolysis at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to December 2021. BP levels 24 h after thrombolysis were analyzed to determine their association with clinical outcomes. BP parameters included mean BP, variability (standard deviation (SD)), and decreased magnitudes. The primary outcome was the 90-day modified Rankin Scale (mRS) scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher mean systolic BP (SBP) was associated with poorer outcomes, with adjusted odds ratios (aORs) of 1.25 (95% CI, 1.03–1.51), 1.23 (1.01–1.49), and 1.25 (1.02–1.52) per 10 mmHg increase within 0–2 h, 2–6 h, and 6–24 h post-thrombolysis, respectively, but not for BP variability and decrease magnitudes. Significant improvements in outcomes were observed when the mean SBP was maintained within the range of 120–140 mmHg during both the 0–2 and 2–6 h periods, with aORs of 0.12 (95% CI, 0.02–0.75) and 0.19 (0.04–0.82), respectively. Larger decreases in SBP within 6 h post-thrombolysis were associated with a lower risk of intracerebral hemorrhage. These findings were consistent across subgroups and sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Achieving sustained low SBP levels (120–140 mmHg within the first 6 h) over 24 h is linked to better outcomes in thrombolyzed AIS patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612497","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":"Correction to “RNF122 Promotes Glioblastoma Growth via the JAK2/STAT3/c-Myc Signaling Axis”","authors":"","doi":"10.1111/cns.70317","DOIUrl":"https://doi.org/10.1111/cns.70317","url":null,"abstract":"<p>Xiao Q, Xue K, Li L, Zhu K, Fu R, Xiong Z, RNF122 Promotes Glioblastoma Growth via the JAK2/STAT3/c-Myc Signaling Axis, CNS Neuroscience &amp; Therapeutics 30, (2024): e70017 10.1111/cns.70017.</p><p>In the original version of our article, there was an error in Figure 6A. Specifically, the representative image of A-172 (oeRNF122 + WP1066) cells in Figure 6A is incorrect. The correct image is provided below. This correction will not affect the results and conclusions.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612499","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":"A Novel Nomogram Integrating Retinal Microvasculature and Clinical Indicators for Individualized Prediction of Early Neurological Deterioration in Single Subcortical Infarction","authors":"Chen Ye,&nbsp;William Robert Kwapong,&nbsp;Le Cao,&nbsp;Hui Xu,&nbsp;Yanan Wang,&nbsp;Yuying Yan,&nbsp;Ruosu Pan,&nbsp;Ruilin Wang,&nbsp;Kun Lu,&nbsp;Lanhua Liao,&nbsp;Tang Yang,&nbsp;Shuai Jiang,&nbsp;Xuening Zhang,&nbsp;Wendan Tao,&nbsp;Junfeng Liu,&nbsp;Bo Wu","doi":"10.1111/cns.70337","DOIUrl":"https://doi.org/10.1111/cns.70337","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Early neurological deterioration (END) is a relatively common occurrence among patients with single subcortical infarctions (SSI). Accurate and early prediction of END in SSI is challenging and could contribute to enhancing prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective observational study enrolled SSI patients who arrived within 24 h from symptom onset at a single center between December 2020 and March 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the predictive model. A nomogram was generated based on multivariate logistic regression analysis to identify potential predictors associated with the risk of END. The performance and clinical utility of the nomogram were generated using Harrell's concordance index, calibration curve, and decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 166 acute SSI patients, 45 patients (27.1%) developed END after admission. The appearance of END is associated with four routine clinical factors (NIHSS score, serum neuron-specific enolase, uric acid, periventricular white matter hyperintensity), and two retinal microvascular indicators (ipsilateral superficial and deep vascular complexes). Incorporating these factors, the nomogram model achieved a concordance index of 0.922 (95% CI 0.879–0.964) and had a well-fitted calibration curve and good clinical application value by DCA. A cutoff value of 203 was determined to predict END via this nomogram.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This novel nomogram exhibits high accuracy in predicting END in SSI patients. It could guide clinicians to identify SSI patients with a high risk of END at an early stage and initiate necessary medical interventions, ultimately leading to a better prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612577","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":"Applications and Predictors of Outcomes Following Stereo-Electroencephalography in Pediatric Patients With Drug-Resistant Epilepsy","authors":"Qingzhu Liu,&nbsp;Chang Liu,&nbsp;Shuang Wang,&nbsp;Taoyun Ji,&nbsp;Yu Sun,&nbsp;Guojing Yu,&nbsp;Yao Wang,&nbsp;Hao Yu,&nbsp;Yuwu Jiang,&nbsp;Xiaoyan Liu,&nbsp;Lixin Cai","doi":"10.1111/cns.70332","DOIUrl":"https://doi.org/10.1111/cns.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to evaluate the role of stereo-electroencephalography (SEEG) in managing pediatric patients with drug-resistant epilepsy. We further explore prognostic factors influencing surgical outcomes following SEEG-guided resective or disconnective surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review was conducted on pediatric patients who underwent SEEG at the Pediatric Epilepsy Center, Peking University First Hospital, between July 2017 and July 2022. Univariate and multivariate analyses identified key predictors for SEEG-guided surgery. Kaplan–Meier survival analysis was employed to estimate the seizure-free rate, and further statistical tests were applied to evaluate factors associated with seizure outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 148 children included in this study, 102 underwent SEEG-guided resective/disconnective surgery. Multivariate regression identified age at surgery (<i>p</i> &lt; 0.05, 95% CI 0.190–0.997) as an independent predictor for selecting resective/disconnective surgery. The seizure-free rate in patients who underwent SEEG-guided surgery was 69.6%. Multivariate regression confirmed that total resection with lesional MRI (<i>p</i> &lt; 0.05, 95% CI 0.012–0.186) and FCD type II (<i>p</i> &lt; 0.05, 95% CI 0.051–0.851) were strong predictors of seizure freedom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SEEG plays a crucial role in pediatric epilepsy surgery, particularly in children under 6 years old. Total resection with lesional MRI and FCD type II was the most favorable prognostic predictor for achieving seizure freedom in children undergoing SEEG-guided surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602506","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":"Sequential Proteomic Analysis Reveals the Key APOE4-Induced Pathological and Molecular Features at the Presymptomatic Stage in Alzheimer's Disease Mice","authors":"Pengju Wei,&nbsp;Kaihua Lin,&nbsp;Xuhui Chen,&nbsp;Cheng Fang,&nbsp;Linhui Qiu,&nbsp;Jun Hu,&nbsp;Junlei Chang","doi":"10.1111/cns.70306","DOIUrl":"https://doi.org/10.1111/cns.70306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) involves a prolonged presymptomatic or preclinical stage with subtle pathological changes. Apolipoprotein E4 (APOE4) is a significant genetic risk factor for AD, yet its specific role at the presymptomatic stage is not fully understood. This study aimed to elucidate the cellular and molecular effects of APOE4 compared to APOE3 on AD progression during the presymptomatic stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated <i>5xFAD</i> AD mice carrying human APOE3 or APOE4 and their non-AD controls. Behavioral tests, immunostaining, quantitative proteomics and phosphoproteomics, Golgi staining, and Western blotting were conducted at 3 or 10 months of age, respectively. Cell culture experiments were performed to assess APOE4's direct impact on neuronal mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>APOE4 significantly increased β-amyloid (Aβ) deposition and microglial activation compared to APOE3 in <i>5xFAD</i> mice at the presymptomatic stage, without aggravating the blood–brain barrier disruption. Proteomic and biochemical analysis revealed strong molecular features of synaptic degeneration and mitochondrial dysfunction associated with APOE4. Notably, APOE4 promoted mitochondrial fusion and mitophagy while inhibiting fission, leading to impaired neuronal energy supply and increased reactive oxygen species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that APOE4 accelerates AD pathologies at the presymptomatic stage by exacerbating Aβ deposition, neuroinflammation, and synaptic degeneration. The study highlights mitochondrial dysfunction as a critical mediator of APOE4-induced AD progression, providing potential targets for early intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612498","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":"Comments on “H4K12 Lactylation-Activated Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury”","authors":"Jieqi Zhang,&nbsp;Kelin He,&nbsp;Ruijie Ma","doi":"10.1111/cns.70339","DOIUrl":"https://doi.org/10.1111/cns.70339","url":null,"abstract":"<p>We read with great interest the recent study by Wang et al. [<span>1</span>] on the role of H4K12 lactylation (H4K12la) in promoting Spp1 transcription and facilitating functional recovery after spinal cord injury (SCI). The work provides novel insights into the relationship between metabolic reprogramming in microglia and neurorepair. By utilizing recombinant Spp1 protein (rSPP1), the authors have demonstrated its significant role in functional recovery, and we believe this study has important implications for spinal cord injury research.</p><p>We would like to offer a few suggestions that could further strengthen the study's reliability and completeness.</p><p>First, regarding the overexpression experiments, the authors used recombinant Spp1 protein (rSPP1) to investigate its effects on functional recovery following SCI. It is crucial to confirm the successful overexpression of Spp1 protein. Given that the half-life of recombinant proteins may vary depending on their properties and the administration route, confirming the protein expression levels at different time points will be essential for understanding its biological effects [<span>2, 3</span>]. We recommend the inclusion of Western blot (WB) results for both the vector group and recombinant Spp1 protein group at multiple time points to verify the expression levels of Spp1, particularly to confirm the duration of stable overexpression. This will help assess whether the overexpression effect of Spp1 is maintained during critical time windows of the experiment, which will strengthen the reliability of the observed functional recovery results.</p><p>Additionally, while the authors conducted separate experiments with neurons and microglia, there was no mention of coculture experiments involving both cell types. We suggest the authors include coculture experiments to investigate the bidirectional interaction between Spp1 in neurons and microglia, particularly how Spp1 may promote neuronal recovery by modulating the activation of microglia. This would offer a more comprehensive understanding of the mechanism by which Spp1 contributes to SCI repair.</p><p>Overall, we commend the authors for their innovative work and believe that their findings significantly advance our understanding of Spp1 in spinal cord injury repair. We look forward to further exploration of Spp1 and its regulatory mechanisms in this context.</p><p>Thank you for considering our suggestions, and we anticipate the continued development and refinement of this important work.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612578","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}