CNS Neuroscience & Therapeutics最新文献

{"title":"Assessing the Impact of Estimated Glucose Disposal Rate (eGDR) on Cognitive Function in Older Adults: A NHANES-Based Machine Learning Study","authors":"Tianyi Wang,&nbsp;Haochen Jiang,&nbsp;Ruwen Zheng,&nbsp;Chuchu Zhang,&nbsp;Xiumei Ma,&nbsp;Yi Liu","doi":"10.1111/cns.70524","DOIUrl":"https://doi.org/10.1111/cns.70524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigates the relationship between estimated glucose disposal rate (eGDR) and cognitive function, with a focus on its potential as a predictive marker for cognitive impairment in older adults. The study also compares eGDR with other insulin resistance (IR) indices, including the triglyceride-glucose index (TyG), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were obtained from the National Health and Nutrition Examination Survey (NHANES) for participants aged ≥ 60 years. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Participants were stratified by eGDR quartiles, and multivariable regression models were applied to evaluate the relationship between eGDR and cognitive impairment. Further analyses included interaction tests, restricted cubic splines (RCS), and machine learning models (LASSO, XGBoost, Random Forest), with performance assessed through ROC curves, decision curve analysis (DCA), and SHAP values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher eGDR levels were significantly associated with improved cognitive scores and a reduced risk of cognitive impairment. For each 1-unit increase in eGDR, cognitive scores improved by 0.095 points, and the odds of cognitive impairment decreased by 7.5%. Quartile analysis revealed the highest eGDR quartile to be associated with better cognitive function when compared with the lowest quartile. Additionally, the eGDR is potentially more predictive of cognitive dysfunction than other infrared indices. The machine learning model confirms the potential clinical utility of the eGDR in predicting cognitive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>eGDR may be a reliable and effective predictor of cognitive function and cognitive impairment risk in older adults. The study suggests that higher eGDR levels may serve as a protective factor against cognitive decline, highlighting the potential importance of managing eGDR for cognitive health, particularly in at-risk populations. Further research, including longitudinal studies and interventions targeting eGDR components, is needed to confirm these findings and explore potential therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624726","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":"Oxytocin Intervention Mitigates Pathological and Behavioral Impairments in APP/PS1 Mice Subjected to Early Social Isolation","authors":"Junjun Li,&nbsp;Yue Li,&nbsp;Zhuoya Wang,&nbsp;Yuan Yao,&nbsp;Dezhong Yao,&nbsp;Ke Chen,&nbsp;Yang Xia","doi":"10.1111/cns.70511","DOIUrl":"https://doi.org/10.1111/cns.70511","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuropsychiatric symptoms, such as anxiety and depression, are prevalent during the prodromal phase of Alzheimer's disease (AD). Social isolation (SI) has been implicated as a potential exacerbating factor for emotional disturbances in AD pathogenesis. Despite the well-established role of oxytocin (OXT) in regulating social behavior and mental health, its function and mechanisms in alleviating AD-related psychiatric symptoms remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We utilized a 12-week SI model to assess its effects on anxiety, depression-like behaviors, and social cognition in early-stage AD mice. Through immunofluorescence, enzyme-linked immunosorbent assay, and 16S rDNA sequencing, we examined the changes in AD pathology and gut microbiota composition induced by SI, as well as the effects of OXT intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that SI markedly intensified anxiety-like behaviors, depression-like phenotypes, and social cognitive impairments in AD mice. Mechanistically, SI resulted in decreased OXT levels and upregulated OXT receptor expression while also exacerbating AD-related pathological features, including increased Aβ plaque deposition, aberrant microglial proliferation, and reduced PSD-95 expression in the prefrontal cortex. Furthermore, SI induced significant changes in gut microbiota composition. OXT intervention demonstrated therapeutic efficacy by mitigating behavioral deficits, alleviating AD-related pathological damage, and restoring gut microbiota homeostasis in SI AD mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results underscore OXT as a promising therapeutic avenue for AD, offering novel insights into treatment strategies and identifying potential therapeutic targets through the restoration of gut homeostasis and mitigation of pathological processes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589658","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":"Identification of the Critical Life-Stage of Obesity Contributing to Brain Functional Networks","authors":"Pei Xiao,&nbsp;Yan Li,&nbsp;Jiayuan Dai,&nbsp;Jingfan Xiong,&nbsp;Jie Mi","doi":"10.1111/cns.70510","DOIUrl":"https://doi.org/10.1111/cns.70510","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Observational studies suggest that obesity impacts brain functional connectivity, but critical developmental periods for these effects remain unclear. Herein, we aimed to investigate the causal relationships between life-course body weight and brain functional connectivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mendelian randomization (MR) was applied to infer the causality between life-course body weight (birth weight [<i>n</i> = 80,745], childhood body mass index [BMI; <i>n</i> = 39,620], and adulthood BMI [<i>n</i> = 322,154]) and 191 resting-state functional magnetic resonance imaging traits (<i>n</i> = 34,691) using genome-wide association data. Linkage disequilibrium score regression and colocalization analysis were conducted to reinforce the causality. Two-step mediation MR, transcriptome-wide association studies, and enrichment analyses were performed to explore the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Adulthood BMI increased neural activity in the frontal lobe (<i>β</i> = 0.078, 95% CI: 0.029 ~ 0.127), whereas childhood BMI reduced functional connectivity between the subcortical-cerebellum and motor or attention network (<i>β</i> = −0.087, 95% CI: −0.144 ~ −0.031). Birth weight decreased the functional connectivity of the central executive or default mode network in the temporal lobe (<i>β</i> = −0.147, 95% CI: −0.217 ~ −0.078). These causalities were consistent with the MR sensitivity analyses and colocalization results. The mediation MR identified neurexophilin-3 as a potential mediator of the causal effect of birth weight on functional connectivity, explaining 27.3% of the total effect (95% CI: 2.6%–52.0%, <i>p</i> = 0.048). Furthermore, transcriptional analysis revealed prioritized genes and pathways that interconnect body weight at different life stages and brain functional connectivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrated distinct life-stage-specific effects of body weight on brain functional networks, highlighting the need for targeted interventions across the life course to mitigate the persistent effect of early-life obesity on brain health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589660","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":"Intracapsular Resection of Thoracic Extradural Schwannomas via the Isthmic Approach: Investigation of Clinical Feasibility With 41 Case Series","authors":"Wei Gao,&nbsp;Xinben Hu,&nbsp;Tianjian Liu,&nbsp;Aiqin Chen,&nbsp;Jingyin Chen,&nbsp;Chi Gu,&nbsp;Guangyu Ying,&nbsp;Qiangwei Wang,&nbsp;Yongjian Zhu","doi":"10.1111/cns.70506","DOIUrl":"https://doi.org/10.1111/cns.70506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Thoracic spinal canal schwannomas can pose surgical challenges when extending into intra- and extra-foraminal regions and the thoracic cavity. This article aims to elucidate the technical nuances and clinical feasibility of the isthmic approach for treating thoracic extradural schwannomas via intracapsular resection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The surgical technique was meticulously outlined, and a retrospective analysis of 41 patients who underwent thoracic schwannoma resection via the isthmic approach between January 2014 and August 2022 was conducted. Parameters including gross total resection (GTR) rate, operative duration, estimated blood loss (EBL), incision length, and postoperative hospital stay were evaluated. Preoperative and postoperative neurosurgical functions were assessed using the modified McCormick functional schema and Visual Analogue Scale (VAS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>All patients achieved GTR, with an operative time of 125.37 ± 45.17 min, an average incision length of 6.56 ± 1.04 cm, and an estimated blood loss of 69.88 ± 86.54 mL. The average hospital stay was 6.76 ± 3.73 days. The VAS score significantly decreased postoperatively (preoperative vs. postoperative: 2.10 ± 0.85 vs. 1.32 ± 0.47, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The isthmic approach via intracapsular resection is a promising method for treating extradural schwannomas extending into intra- and extra-foraminal regions. This approach enhances total tumor resection rates, preserves spinal stability, and significantly reduces operative duration, incision length, and blood loss.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589659","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":"Surgery May Be a Major Contributor for Postoperative Delirium in Patients With Elective Thoracic Aortic Aneurysm Procedures","authors":"Lucas G. Fernandez,&nbsp;Weiran Shan,&nbsp;Abdullah S. Terkawi,&nbsp;Sandeep Yerra,&nbsp;Zhiyi Zuo","doi":"10.1111/cns.70509","DOIUrl":"https://doi.org/10.1111/cns.70509","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Postoperative delirium (POD) is relatively common and is associated with poor outcomes. Age is a risk factor for POD. This single-center observational study is designed to determine whether surgery is a major contributor to the development of POD and inflammatory response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with elective procedures to repair thoracic aortic aneurysm were recruited to the study. Confusion Assessment Method was used to assess POD. Their blood and cerebrospinal fluids were harvested for analysis of inflammatory and neuronal injury indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 67 patients were included in this study: 32 had stent placement under general anesthesia and 35 had open surgery to repair the aneurysm. No patients in the stent placement group had POD, but 9 patients in the open surgery group had POD (25.7%). Patients with POD had a lower body temperature at the end of surgery than patients without POD [36.3°C (35.7°C–36.6°C) vs. 36.7°C (36.3°C–37.0°C), <i>p</i> = 0.046]. This parameter was identified as a risk factor for POD. Patients in the open surgery group had increased interleukin 1β and neurofilament light chain in the blood. However, there was no change in these biomarkers in the cerebrospinal fluids at 10 and 24 h after surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest that surgery is a major contributor to POD, inflammatory response, and neuronal injury. Low body temperature at the end of surgery is a potential risk factor for POD in patients with open repair for thoracic aortic aneurysm.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581834","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":"Downregulation of Mfn2 Contributes to Chronic Postsurgical Pain via Inducing the Pyroptosis of GABAergic Neurons in the Spinal Cord","authors":"Yingjie Hu,&nbsp;Xiao He,&nbsp;Hu Zang,&nbsp;Yuye Chen,&nbsp;Li Li,&nbsp;Tongtong Liu,&nbsp;Li Wan,&nbsp;Chang Zhu,&nbsp;Wenlong Yao","doi":"10.1111/cns.70508","DOIUrl":"https://doi.org/10.1111/cns.70508","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic postoperative pain (CPSP) is a significant public health issue due to the complex pathophysiological mechanism. Existing evidence has pointed out that the loss of gamma-aminobutyric acid-ergic (GABAergic) neurons played a critical role in various neuropathic pain models. Previous studies also found that pyroptosis-mediated neuroinflammation was involved in neuropathological pain. However, it remains unclear what the relationship is between pyroptosis and the loss of spinal GABAergic neurons in CPSP. This study aimed to investigate the role and mechanism of GABAergic neuron pyroptosis in CPSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used skin/muscle incision and retraction (SMIR) to establish the CPSP model in rats. Mechanical allodynia was assessed using the Von Frey test. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, biochemical assay, and transmission electron microscope (TEM) were employed to investigate the role and mechanism of GABAergic neuron pyroptosis during CPSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed the pyroptosis of GABAergic neurons in the spinal cord following SMIR. Intrathecal administration of the GSDMD inhibitor decreased the pyroptosis of GABAergic neurons in the spinal cord and reversed SMIR-induced mechanical allodynia. In addition, we found that SMIR induced a significant decrease in the level of Mfn2 in the neurons, accompanied by mitochondrial dysfunction and reactive oxygen species (ROS) accumulation in SMIR rats. Intrathecal injection of the Mfn2 activator reduced mitochondrial dysfunction and ROS, alleviated the pyroptosis of GABAergic neurons in the spinal cord, which alleviated the SMIR-induced mechanical allodynia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that downregulation of Mfn2 leads to mitochondrial dysfunction and ROS accumulation, which promotes the pyroptosis of spinal GABAergic neurons and the development of chronic pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582120","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 Meta-Analysis and Systematic Review of the Effects of Sensory Modulation Treatments for Neurogenic Oropharyngeal Dysphagia","authors":"Meng Dai,&nbsp;Ivy Cheng,&nbsp;Ayodele Sasegbon,&nbsp;Wanqi Li,&nbsp;Shaheen Hamdy","doi":"10.1111/cns.70452","DOIUrl":"https://doi.org/10.1111/cns.70452","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oropharyngeal sensory stimulation has been applied broadly in clinical dysphagia management, but evidence remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to determine its effectiveness in treating neurogenic dysphagia (ND).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>A systematic review and meta-analysis was conducted using studies from PubMed, EMBASE (via Ovid), CINAHL, Web of Science, and the Cochrane Library, searched up to January 2025. We included randomized controlled trials (RCT) comparing sensory stimulations, including electrical and gustatory stimulation, with sham controls or placebo. The outcome measurements included swallowing scales based on clinical and instrumental evaluations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 16 RCTs (620 participants) in the meta-analysis. Overall, sensory stimulation significantly improved ND (<i>n</i> = 17, SMD [95% CI] = 0.80 [0.41, 1.20], <i>p</i> &lt; 0.001; <i>I</i>² = 71%). Subgroup analysis revealed that the pooled effect size remained significant for electrical stimulation (<i>n</i> = 14, SMD [95% CI] = 0.79 [0.36, 1.23], <i>p</i> &lt; 0.01; <i>I</i>² = 64%), but not for gustatory stimulation (<i>n</i> = 3, SMD [95% CI] = 0.76 [−1.68, 3.20], <i>p</i> = 0.31; <i>I</i>² = 90%). The pooled effect sizes for sensory stimulation were significant for both swallowing measurements (<i>n</i> = 14, SMD [95% CI] = 0.75 [0.27, 1.23], <i>p</i> &lt; 0.01; <i>I</i>² = 76%) and acceleration of decannulation (<i>n</i> = 3, OR [95% CI] = 6.47 [1.10, 38.04], <i>p</i> = 0.05; <i>I</i>² = 3%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Oropharyngeal sensory stimulation improves swallowing function and decannulation in ND, with minimal adverse effects. While electrical stimulation shows clear benefits, gustatory effects remain inconclusive. Further studies are warranted to optimize protocols and confirm efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574005","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":"rTMS Improves Cognition in Patients With Self-Limited Epilepsy With Centrotemporal Spikes With Electrical Status Epilepticus in Sleep via Increase of the Sleep Spindle","authors":"Yixian Han,&nbsp;Jing Gao,&nbsp;Yongkang Zhou,&nbsp;Jiahui Deng,&nbsp;Huajun Yang,&nbsp;Xiongfei Wang,&nbsp;Jing Wang,&nbsp;Yujiao Yang,&nbsp;Jie Ren,&nbsp;Lingling Chen,&nbsp;Minghui Wang,&nbsp;Qinqin Deng,&nbsp;Haidan Wang,&nbsp;Mengyang Wang,&nbsp;Tianfu Li","doi":"10.1111/cns.70501","DOIUrl":"https://doi.org/10.1111/cns.70501","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) and electrical status epilepticus in sleep (ESES) lead to cognitive impairment. However, therapeutic options are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The <b>s</b>leep spindle is a biomarker of cognitive dysfunction in patients with SeLECTS. This study aimed to explore whether the sleep spindle is linked to the outcome of repetitive transcranial magnetic stimulation (rTMS) in patients with SeLECTS with ESES.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine patients with SeLECTS with ESES underwent low-frequency rTMS (≤ 1 Hz) or continuous theta burst stimulation (cTBS) for 10 days. To assess the clinical efficacy and alteration in the sleep spindle, EEG recordings were performed both before and after rTMS. A machine learning algorithm YASA was used to calculate the coupling of the sleep spindle and slow waves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>75% of patients remained seizure-free for 6 months after rTMS. The spike–wave index (SWI) decreased significantly after rTMS compared with the baseline. The sleep spindle significantly increased in all patients at 3 months and 6 months after rTMS (<i>p</i> = 0.002). Both IQ and MQ improved significantly at 6 months after rTMS. Improvement of IQ and increase of the sleep spindle was significantly positively correlated (<i>p</i> = 0.035). The mean probability of the sleep spindle coupling in the slow wave “up” state increased from 28% to 55%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion(s)</h3>\u0000 \u0000 <p>Increase of the sleep spindle and the mean probability of the sleep spindle coupling in the slow wave “up” state might be a potential mechanism for cognition improvement in patients with SeLECTS with ESES.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573671","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":"Dehydrocostus Lactone Inhibits Microglia-Mediated Neuroinflammation by Targeting CYP2A6 to Improve Ischemic Brain Injury","authors":"Xin Shu,&nbsp;Xinxin Zou,&nbsp;Jingxuan Zhang,&nbsp;Xu Fang,&nbsp;Xinyu Wang,&nbsp;Hui Wu,&nbsp;Xuan He,&nbsp;Dujuan Sha","doi":"10.1111/cns.70502","DOIUrl":"https://doi.org/10.1111/cns.70502","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroinflammation is an important factor in ischemic stroke. Dehydrocostus lactone (DHC) plays an anti-inflammatory role in certain diseases. However, the role of DHC in neuroinflammation after ischemic stroke remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DHC was administered to lipopolysaccharide (LPS)-treated BV2 cells and a middle cerebral artery occlusion (MCAO) model to detect the levels of inflammatory factors using quantitative real-time PCR, western blotting, and behavioral tests. Morphological changes in microglia were observed using immunofluorescence. The Swiss Target Prediction database was used to predict the target of DHC. Finally, a specific inhibitor of the target protein was used to investigate its potential synergistic role in neuroinflammation, both with and without being combined with DHC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of inflammation-related factors both in vivo and in vitro was improved by DHC, and the neurological deficits in mice after MCAO were improved in the DHC administration group. In addition, the Swiss Target Prediction showed that CYP2A6 was a target of DHC. Specifically, the combination of DHC with the CYP2A6 inhibitor showed that DHC exerts anti-inflammatory effects in a CYP2A6-dependent manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Mechanistically, DHC inhibited neuroinflammation by binding to the target CYP2A6. Our study suggests that DHC is a promising new strategy for treating ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558284","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":"Hyperglycemia Aggravates 6-Hydroxydopamine-Induced Neuronal Ferroptosis via SLC7A11-Dependent Pathway in Diabetic PD Rat Model","authors":"Ya Zhao,&nbsp;Dan Wang,&nbsp;Yanwei Wang,&nbsp;Dan Mu,&nbsp;Lang Qu,&nbsp;Rong Li","doi":"10.1111/cns.70487","DOIUrl":"https://doi.org/10.1111/cns.70487","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The epidemiological link between diabetes mellitus (DM) and Parkinson's disease (PD) is well-established, but the mechanistic basis remains unclear. Chronic hyperglycemia, a hallmark of DM, may exacerbate PD pathogenesis, though the underlying molecular pathways are poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using an integrative approach combining metabolomic profiling, proteomic analysis, and molecular characterization in vitro and in vivo models, we investigated the role of the cystine/glutamate antiporter system in glucose-induced neuronal vulnerability. SLC7A11 expression was genetically restored, and adeno-associated viral vectors delivered SLC7A11 to the nigrostriatal pathway in a streptozotocin-induced diabetic PD rat model to evaluate neuroprotection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic high glucose impaired SLC7A11 function, reducing cystine uptake and depleting intracellular glutathione in dopaminergic neurons, increasing susceptibility to 6-hydroxydopamine-induced ferroptosis. SLC7A11 restoration rescued neuronal viability, restored redox homeostasis, and attenuated motor deficits and dopaminergic neuron loss in the diabetic PD model. Mechanistically, SLC7A11 enhanced glutathione synthesis and suppressed ferroptosis signaling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chronic hyperglycemia disrupts the cystine/SLC7A11/glutathione axis, accelerating neuronal degeneration and linking DM to PD susceptibility. SLC7A11 emerges as a potential therapeutic target to mitigate neurodegeneration in diabetic individuals at risk for PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550874","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}