CNS Neuroscience & Therapeutics最新文献

{"title":"A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice","authors":"Zhixin Wu, Dongkun Xie, Jing Zhao, Jianshuai Zhao, Huiqing Liu, Dong Xing, Tingting Gu, Yaru Guo, Dan Wang, Zhihong Lu, Hailong Dong, Junlong Zhao, Jiao Deng","doi":"10.1111/cns.70454","DOIUrl":"https://doi.org/10.1111/cns.70454","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Perioperative cognitive disorder (PND) affects up to 31% of surgical patients. Although clinical studies have identified a variety of risk factors, no effective prevention has been developed. From our previous cohort of PND patients, several single-nucleotide polymorphism (SNP) sites on <i>ctnna2</i> were identified. The current study aims to decipher the role and regulatory mechanism of <i>ctnna2</i> in the PND model and to develop decoy oligodeoxynucleotides (decoy) for the possible prevention of PND.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Both mice model (exploratory laparotomy+isoflurane) and the neuronal model (TNFα+isoflurane, T + I) for PND were used. Bioinformatic research was utilized to identify transcriptive active areas on <i>ctnna2</i>, <i>foxo3</i> sequence, and to predict possible transcriptional factors for regulation. Molecular biological techniques were used to decipher the regulatory mechanism and specific sites of the Sirt1-foxo3-ctnna2 axis in the development of PND. Finally, an decoy targeting the Foxo3-ctnna2 interaction was designed and tested for effectiveness in PND.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that the SNP rs12472215 is located at a newly defined enhancer region within the <i>ctnna2</i> intron that can be regulated by Foxo3 in the human genome. The rs12472215 A>T mutation potentiates Foxo3's transcriptive inhibitory effect on <i>ctnna2</i>. Experimental laparotomy in mice revealed that hippocampal Foxo3 upregulation and α-N-catenin reduction are involved in PND development. ChIP-PCR deciphered two regulatory sites (R1 and R2) of Foxo3 on <i>ctnna2</i> in the mice that are strengthened by T + I. siAscl1 abolished the rescue effect of carbenoxolone (CBX, Foxo3-specific inhibitor) on α-N-catenin expression in the T + I model, indicating that Foxo3 inhibits <i>ctnna2</i> transcription indirectly through Ascl1. Reduction of Sirt1 increased acetyl-Foxo3, which enhanced its stability in PND. Sirt1 activation reduced Foxo3 expression, acetyl-Foxo3 level, and rescued α-N-catenin expression in T + I stimulated neurons. More importantly, the new decoy disturbing Foxo3-ctnna2 interaction effectively prevents α-N-catenin reduction, CA1 pyramidal neuron morphological change, electrophysiological dysfunction, and improves cognitive deficit in PND mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results provided a new revenue for identifying targets and developing interventions for PND. The decoy, due to its specificity and short acting ti","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905553","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":"Effective Connectivity Predicts Surgical Outcomes in Temporal Lobe Epilepsy: A SEEG Study","authors":"Xu Hu,&nbsp;Yuan Yao,&nbsp;Baotian Zhao,&nbsp;Xiu Wang,&nbsp;Zilin Li,&nbsp;Wenhan Hu,&nbsp;Chao Zhang,&nbsp;Kai Zhang","doi":"10.1111/cns.70563","DOIUrl":"https://doi.org/10.1111/cns.70563","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Temporal lobe epilepsy (TLE), the most common type of drug-resistant epilepsy (DRE), has a postoperative seizure-free rate of ~70%. Furthermore, precisely localizing the epileptogenic zone and determining the surgical resection area have been established as the key factors influencing surgical outcomes. Herein, we innovatively coupled the surgical resection area with characteristics of effective connectivity via intracranial electroencephalography (iEEG) to predict patients' surgical prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study involved 56 patients who underwent TLE surgery and were followed up for over 1 year. All patients underwent stereo-electroencephalography (SEEG) electrode implantation and single-pulse electrical stimulation (SPES) tests. After comparing patients' RMS value of N1/N2 (Z-score standardized) from cortico-cortical evoked potentials (CCEP) with different surgical outcomes, an interpretable machine learning (ML) model based on support vector machine (SVM) for predicting patients' surgical prognosis was constructed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with various surgical outcomes exhibited differences in effective connectivity. Furthermore, compared to the seizure-free group (Engel I), patients in the nonseizure-free group (Engel II-IV) exhibited stronger connectivity between the seizure onset zone (SOZ) and regions outside the surgical resection area. The nonseizure-free group also exhibited stronger connectivity between the surgical resection area and regions outside the resection area. Our prediction model demonstrated high-accuracy performance, with accuracy and area under the curve (AUC) values of 0.800 and 0.893, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study confirmed the potential value of integrating the surgical resection area and effective connectivity characteristics in predicting patients' surgical outcomes; offering a novel approach that could be leveraged to precisely determine the surgical resection area and improve TLE patients' surgical prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897410","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":"Regulation of Somatosensory Temporal Discrimination Threshold Through Motor Training: An EEG and Kinematics Study","authors":"Jinyan Zhang,&nbsp;Wangjun Zou,&nbsp;Binbin Gao,&nbsp;Jinglong Wu,&nbsp;Zhilin Zhang,&nbsp;Jian Zhang,&nbsp;Luyao Wang,&nbsp;Tianyi Yan","doi":"10.1111/cns.70564","DOIUrl":"https://doi.org/10.1111/cns.70564","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Motor training enhances somatosensory temporal discrimination threshold (STDT), but the distinct neural mechanisms underlying actual execution versus motor imagery remain unclear. This study aimed to compare the effects of ball-rotation training (BRT; actual execution) and visual-guided imagery (VGI; motor imagery) on STDT, kinematic performance, and neurophysiological plasticity in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight right-handed participants were randomized into four groups: BRT (actual execution), VGI (motor imagery without movement), tactile control (simple gripping), and no-intervention control. Over seven days, participants underwent pre-/post-training assessments including kinematic analysis, STDT measurement, power spectral analysis and somatosensory-evoked potentials (SEPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BRT significantly enhanced motor performance (83% score increase vs. 21% in controls, <i>p</i> &lt; 0.001) and movement speed (37% cycle time reduction vs. 12%–16% in others, <i>p</i> &lt; 0.001), with partial transfer to the untrained hand. Both interventions reduced STDT but at distinct locations: BRT selectively improved index finger discrimination (64.02 ms → 43.75 ms, <i>p</i> = 0.007), while VGI enhanced palm sensitivity (73.43 ms → 61.13 ms, <i>p</i> = 0.003). Neurophysiologically, SEPs revealed increased spatial inhibition ratio (SIR) plasticity in both BRT and VGI (<i>p</i> &lt; 0.001), correlating with STDT gains. EEG demonstrated BRT-induced gamma-band power increases in parietal regions and theta-band elevations in prefrontal cortex, whereas VGI modulated delta-band activity in ipsilateral parietal cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Actual execution (BRT) and motor imagery (VGI) enhance STDT through distinct neuroplastic mechanisms: BRT optimizes sensorimotor integration via parietal gamma/prefrontal theta oscillations, while VGI relies on ipsilateral parietal delta modulation. These findings underscore the role of cortical reorganization in motor learning and support tailored rehabilitation strategies for neurological disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897661","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":"Factors Influencing Hormone Remission in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors With Residual Tumor: A Retrospective Cohort Study","authors":"Yangyang Wang,&nbsp;Li Ma,&nbsp;Chuanbao Zhang,&nbsp;Shunchang Ma,&nbsp;Guijun Jia,&nbsp;Wang Jia,&nbsp;Xiudong Guan","doi":"10.1111/cns.70574","DOIUrl":"https://doi.org/10.1111/cns.70574","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growth hormone-secreting pituitary neuroendocrine tumors (GH-secreting PitNETs) pose significant health risks due to hormone-related complications. Despite transsphenoidal surgical resection being the primary treatment, complete removal is often infeasible due to invasive growth patterns, leading to postoperative tumor residuals and uncertain hormone remission outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 458 patients with GH-secreting PitNETs who underwent surgery at Beijing Tiantan Hospital. Data on preoperative hormone levels, MRI scans, and histopathological features were analyzed. Tumor segmentation, intratumor heterogeneity (ITH) scores, and subcluster clustering based on MRI data were computed using radiomic features, while multivariate analyses determined factors influencing hormone remission. Single-cell data from four GH-type pituitary adenomas were collected from public databases to explore ITH in GH1 gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Postoperative hormone remission was achieved in 61 of 144 patients (42.4%) with residual tumors. Univariate analysis demonstrated that in cases with tumor residuals, preoperative hormone levels, tumor resection rates, residual tumor volume, tumor residual location, residual-tumor proximity to the internal carotid artery, and MRI-based tumor heterogeneity were associated with hormone remission. Among these factors, preoperative hormone levels (10–30 ng/mL vs. ≤ 10 ng/mL: OR: 0.48, 95% CI 0.20–1.19, <i>p</i> = 0.115; &gt; 30 ng/mL vs. ≤ 10 ng/mL: OR: 0.13, 95% CI: 0.04–0.36, <i>p</i> &lt; 0.001), tumor resection rate (OR: 18.29, 95% CI: 2.08–160.97, <i>p</i> = 0.009), and tumor heterogeneity as measured by the ITH score (OR: 1.06, 95% CI: 1.00–1.12, <i>p</i> = 0.042) were independent predictors of hormone remission in cases with residual tumors. Moreover, single-cell data showing highly variable GH1 expression within the same patient reveal ITH in hormone expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preoperative GH levels, tumor resection rates, and ITH scores independently predict hormone remission in GH-secreting PitNETs with residuals. This will provide intraoperative decision-making guidance on how to achieve the maximum possible hormone remission with residual tumors when complete tumor resection is not feasible.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894279","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":"T Cell Involvement in Neuroinflammation After Traumatic Brain Injury: Implications for Therapeutic Intervention","authors":"Mitchell D. Kilgore,&nbsp;Yuwen Xiu,&nbsp;Yinghua Jiang,&nbsp;Yingjie Wang,&nbsp;Mengxuan Shi,&nbsp;Di Zhou,&nbsp;Thin Sein,&nbsp;Sammy J. Vodovoz,&nbsp;Danni Wang,&nbsp;Aaron S. Dumont,&nbsp;Aimee Aysenne,&nbsp;Ning Liu,&nbsp;Xiaoying Wang","doi":"10.1111/cns.70580","DOIUrl":"https://doi.org/10.1111/cns.70580","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) is a leading cause of death and disability across all age groups worldwide. After primary mechanical head injury, a cascade of molecular changes and immunological responses occur that are necessary for supporting tissue repair but also exacerbate the secondary loss of tissue caused by excessive neuroinflammation. To date, there are no targeted treatments that ameliorate the pathological neuroinflammation that is responsible for propagating secondary injury after TBI. Recent works have highlighted the adaptive immune system's response to TBI, with mounting evidence suggesting that T cells play a critical yet understudied role in propagating secondary injury while also potentially supporting reparative processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We critically review the current literature to discuss the diverse functionality of T cells in TBI including the temporospatial characteristics of their response, mechanisms of their activation, and their contributions to the overall neuroinflammatory profile. Consideration is given for additional pathological factors that may further alter these properties. We additionally summarize previous reports of therapeutic T cell modulation in this setting and identify approaches warranting additional investigation. Finally, we discuss major gaps in the existing literature and recommend future research perspectives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Evidence suggests several aspects of the T cell response to TBI may serve as beneficial therapeutic targets for limiting secondary injury. Additional translational investigations are warranted and may support the development of effective therapeutic strategies for treating patients post-head trauma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897512","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":"Assessment of Dysphagia in Chinese Cohort of Angelman Syndrome: An Observational Study","authors":"Yumeng Chen,&nbsp;Yanna Wang,&nbsp;Yi Zhang,&nbsp;Jun Wang,&nbsp;Xiaonan Du,&nbsp;Tianqi Wang,&nbsp;Yi Wang,&nbsp;Hao Zhou","doi":"10.1111/cns.70587","DOIUrl":"https://doi.org/10.1111/cns.70587","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to identify the prevalence and risk factors of dysphagia in a Chinese cohort of Angelman syndrome (AS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A structured questionnaire was used to assess the status of patients in a Chinese cohort of AS. Swallowing function was evaluated using the Pediatric Eating Assessment Tool-10, with gastrointestinal symptoms quantified via the Six-item Gastrointestinal Severity Index (6-GSI). To identify potential risk factors, univariable and multivariate logistic regression was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 490 patients with AS (median 6 years, interquartile range 4 years), the molecular subtypes of 75.7% of cases were deletions of 15q11–q13. The prevalence of dysphagia reached 56.1%. Patients with dysphagia exhibited lower BMI values compared to nondysphagia cases (15.31 ± 2.87 vs. 15.92 ± 2.91 kg/m², <i>p</i> = 0.021). Multivariate logistic regression analysis identified that uniparental paternal disomy (UPD) was associated with lower odds of dysphagia compared with deletions of 15q11–q13 (OR = 0.34, <i>p</i> = 0.016). Comorbid sleep disorders (OR = 1.79, <i>p</i> = 0.007), gastrointestinal disorders (OR = 1.89, <i>p</i> = 0.003), and increased 6-GSI scores (OR = 1.16, <i>p</i> = 0.044) showed associations with higher odds of dysphagia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Over half of Chinese patients with AS experience dysphagia, with UPD moderating risk and comorbidities amplifying susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894297","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":"Cannabinoid Receptors CB1 and CB2 Activation Restores Hippocampal Lipid Profiles and Alleviates Autism-Like Behaviors in Valproic Acid-Induced ASD Rats","authors":"Haoran Wang,&nbsp;Mengyuan Zhang,&nbsp;Sen Yang,&nbsp;Yi Jiang,&nbsp;Lijie Wu,&nbsp;Caihong Sun","doi":"10.1111/cns.70591","DOIUrl":"https://doi.org/10.1111/cns.70591","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Emerging evidence suggests lipid metabolism dysregulation contributes to autism spectrum disorders (ASD), with the endocannabinoid system (cannabinoid receptors CB1R/CB2R) implicated in lipid homeostasis. This study investigated whether CB1R/CB2R activation improves hippocampal lipid metabolism and ASD-like behaviors in a valproic acid (VPA)-induced ASD rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male offspring from dams exposed to VPA (600 mg/kg, i.p.) received the CB1R agonist ACPA (0.1 mg/kg) or the CB2R agonist AM1241 (3 mg/kg) from postnatal days 21–27. ASD-like behaviors (marble burying, self-grooming, social interaction, open-field tests) and hippocampal lipid profiles (UPLC-MS/MS) were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VPA-exposed rats displayed heightened repetitive behaviors, social deficits, and hyperactivity, all significantly alleviated by ACPA and AM1241. Lipidomics revealed marked reductions in hippocampal phosphatidylcholines, lysophosphatidylcholines, fatty acids, sphingomyelins, ceramides, and phosphatidylethanolamines in VPA rats. Both agonists restored lipid levels to near normal, comparable to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CB1R/CB2R activation ameliorates behavioral abnormalities and rectifies hippocampal lipid dysregulation in VPA-induced ASD models, highlighting cannabinoid receptors as potential therapeutic targets for ASD-associated metabolic disturbances.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894296","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":"Oseltamivir Phosphate Modulates CD24-Siglec-G/10 Interaction to Suppress Microglial-Driven Neuroinflammation After Cardiac Arrest","authors":"Yushu Chen,&nbsp;Ying Liu,&nbsp;Na Li,&nbsp;Ling Wang,&nbsp;Peijuan Li,&nbsp;Zhangping Sun,&nbsp;Dongping Yu,&nbsp;Ziren Tang,&nbsp;Ping Gong","doi":"10.1111/cns.70495","DOIUrl":"https://doi.org/10.1111/cns.70495","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In cardiac arrest (CA) patients undergoing cardiopulmonary resuscitation (CPR), neuroinflammation following return of spontaneous circulation (ROSC) contributes to brain ischemia/reperfusion injury and neurological dysfunction. Recent evidence suggested that neuraminidase could exacerbate inflammatory responses by disrupting CD24-Siglec-G/10 immune checkpoint axis. As a neuraminidase inhibitor, oseltamivir phosphate (OP) holds potential for immunomodulation beyond its antiviral use. We aimed to investigate the impact and mechanism of OP on neuroinflammation regulation after ROSC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male pigs were randomized into the sham control group, CPR, and CPR + OP group. CA was induced in pigs through 8 min of untreated ventricular fibrillation. Brains were harvested for assessing serum inflammatory markers and neuronal damage at 24 h after ROSC. BV2 microglial underwent oxygen–glucose deprivation/reperfusion (OGD/R). Effects of OP on inflammatory responses, NF-κB activation, cell viability, and the CD24-Siglec-G/10 interaction were evaluated using immunofluorescence, immunoprecipitation, molecular, and biochemical assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo, OP attenuated pig cerebral microglial activation and neuronal integrity with attenuated neuroinflammation, alongside time-dependent neuraminidase activity increases. In vitro, OP suppressed OGD/R-induced microglial NF-κB activation, reduced pro-inflammatory cytokine levels, and preserved CD24-Siglec-G interaction, correlating with diminished neuraminidase release.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>OP as a repurposed immunomodulator that suppresses microglial-driven neuroinflammation after CA by preserving sialylation-dependent CD24-Siglec-G/10 interaction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881516","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":"Electroacupuncture Improves Microglial Polarization Induced-Inflammation by Regulating the TGF-β/Smad-3 Signaling Pathway in Ischemic Stroke Mice","authors":"Guoqiang Yang,&nbsp;Liulu Zhang,&nbsp;Yanlin Yuan,&nbsp;Maryam Mazhar,&nbsp;Dechou Zhang,&nbsp;Yong Liu,&nbsp;Guiquan Chen,&nbsp;Xuehui Fan","doi":"10.1111/cns.70567","DOIUrl":"https://doi.org/10.1111/cns.70567","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the mechanisms underlying the therapeutic effects of electroacupuncture (EA) at the Dazhui (GV14) and Baihui (GV20) acupoints in the treatment of ischemic stroke (IS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>The therapeutic efficacy of EA was evaluated using a middle cerebral artery occlusion (MCAO) mouse model. Neurological function was assessed through behavioral assessments, and infarct volume was measured using magnetic resonance imaging. Techniques such as immunofluorescence and western blotting were employed to analyze neural injury recovery, neuroinflammation, microglia/macrophage activation and polarization, as well as alterations in the TGF-β/Smad3 signaling pathway. Our findings demonstrated that EA significantly improved neurological function and reduced infarct volume in MCAO mice. Furthermore, EA attenuated neuroinflammation by suppressing the polarization of microglia toward the pro-inflammatory M1 phenotype. Additionally, EA decreased the expression of TGF-β and Smad3 proteins following MCAO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EA may inhibit the M1 polarization of microglia/macrophages and provide a protective effect against ischemic brain injury by modulating the TGF-β/Smad-3 signaling pathway. These findings suggest that EA could be a potential therapeutic strategy for IS treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869524","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":"PRG-1 Relieves Neonatal Stimuli-Induced Hyperalgesia and Anxiety via Stage-Specific Synapse Remodeling","authors":"Wenyu Zhang,&nbsp;Yan Li,&nbsp;Guangda Liang,&nbsp;Qingmei Li,&nbsp;Zhouyi Song,&nbsp;Song Cao,&nbsp;Zhi Xiao,&nbsp;Xingfeng Liu","doi":"10.1111/cns.70560","DOIUrl":"https://doi.org/10.1111/cns.70560","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Neonatal repetitive noxious stimuli (RNS), to mimic early-life repetitive pain exposure, induce persistent hyperalgesia, anxiety-like behaviors and postoperative pain sensitization that endure into adulthood. These long-term neurobehavioral abnormalities are associated with impaired cognitive, emotional, and psychosocial functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We established a neonatal RNS rat model through repetitive needle pricks to all four limbs of neonatal rats and investigated the effects of hippocampal PRG-1 and synaptic remodeling at different stages in RNS rat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study demonstrates that hippocampal PRG-1 dynamically modulates RNS-induced hyperalgesia and anxiety through stage-specific regulation of AMPAR GluR1/GluR2 and NMDAR GluN2A/GluN2B trafficking, which leads to synaptic remodeling via altered dendritic synaptic morphology and synaptic transmission efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that PRG-1 relieves RNS-induced persistent hyperalgesia, anxiety, and pain-perception memory via synapse remodeling at different stages. Targeting PRG-1-mediated synaptic remodeling may provide a novel neuroprotective strategy for preventing chronic pain comorbidities with anxiety disorders following early-life pain exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861588","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}