CNS Neuroscience & Therapeutics最新文献

{"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":"Multi-Target Repetitive Transcranial Magnetic Stimulation Improves Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial","authors":"Zixuan Zhang,&nbsp;Danyang Liu,&nbsp;Wenjing Song,&nbsp;Jinyu Li,&nbsp;Xi Wang,&nbsp;Peixiao Yin,&nbsp;Yuning Liu,&nbsp;Min Xu,&nbsp;Fujia Li,&nbsp;Yumeng Li,&nbsp;Guiyun Cui,&nbsp;Wei Zhang","doi":"10.1111/cns.70582","DOIUrl":"https://doi.org/10.1111/cns.70582","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this randomized, double-blind, sham-controlled trial, we investigated the efficacy of multi-target 10-Hz rTMS targeting both M1 and SMA in alleviating freezing of gait (FOG) in Parkinson's disease (PD) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty-four PD-FOG patients were randomly assigned (1:1:1:1) to four groups: M1 and SMA group, M1 group, SMA group, and sham group. rTMS was administered once daily for 10 consecutive days. Assessments were conducted at baseline (T0), after the final session (T1), and 30 days posttreatment (T2), using the FOG-Q, UPDRS-III, Timed Up and Go (TUG) Test, Standing-Start 180° Turn (SS-180) Test, and measures of emotion and cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Application of 10-Hz rTMS to bilateral M1 or SMA significantly reduced FOG severity, improved motor function, and alleviated emotional disturbances in PD patients, with effects lasting at least 1 month. Compared to single-target stimulation, multi-target stimulation of M1 and SMA high-frequency rTMS showed more pronounced therapeutic effects across these outcomes. However, no significant cognitive improvements were observed in either the real or sham stimulation groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results of this study indicate that bilateral M1 and SMA 10-Hz rTMS is a promising therapeutic approach, providing new possibilities for clinical treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891559","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}

{"title":"IL-4-JAK1-STAT6 Pathway Mediates Electroacupuncture's Effect on Microglial M2 Polarization to Treat Inflammatory Bowel Disease With Comorbid Depression","authors":"Sihui Cao,&nbsp;Jingjing Yang,&nbsp;Lin Chen,&nbsp;Zuqiang Li,&nbsp;Lv Jia,&nbsp;Yuxiang Huang,&nbsp;Zhanwei Xu,&nbsp;Penghui Lu,&nbsp;Jin Liu,&nbsp;Qiong Liu,&nbsp;Mi Liu","doi":"10.1111/cns.70572","DOIUrl":"https://doi.org/10.1111/cns.70572","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Depression is prevalent in inflammatory bowel disease (IBD) and linked to neuroinflammation. However, the underlying mechanisms remain unclear. Therefore, we investigated the efficacy of electroacupuncture in mice with IBD and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An IBD mouse model of depression was established using 2.0% dextran sodium sulfate (DSS). After electroacupuncture, general condition and behavior were evaluated. Colon morphology was observed using hematoxylin and eosin staining. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. Microglial activation was measured using immunofluorescence. Hippocampal protein expression was assessed using Western blotting and real-time fluorescence quantitative polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DSS-induced model mice exhibited significant depression-like behaviors and colon pathology. Serum and colon IL-1β expression was elevated (<i>p</i> &lt; 0.01), while IL-4, IL-10, and TGF-β1 expression was decreased (<i>p</i> &lt; 0.01 or <i>p</i> &lt; 0.05). Hippocampal microglial activation was evident, with increased IL-1β expression (<i>p</i> &lt; 0.01) and reduced IL-4, IL-10, TGF-β1, JAK1, STAT6, and p-STAT6 expression (<i>p</i> &lt; 0.01 or <i>p</i> &lt; 0.05). Electroacupuncture resolved these changes; though its effects were significantly weakened after IL-4 and p-STAT6 inhibitor administration (<i>p</i> &lt; 0.01 or <i>p</i> &lt; 0.05). Transcriptomic sequencing of hippocampal tissue indicates that pro-inflammatory pathways such as TNF/NF-κB/mTOR are activated in the model group. Electroacupuncture can activate the IL-4–mediated JAK–STAT signaling pathway, inhibit the activation of pro-inflammatory signaling pathways, upregulate neuroprotective genes such as Slc2a3, Mef2d, and Jak1, and exert anti-inflammatory effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IL-4-JAK1-STAT6 signaling may be an important pathway in mediating the efficacy of electroacupuncture in IBD with comorbid depression, particularly promoting microglial M2 polarization and improving neuroinflammation.</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.70572","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861838","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":"Microglia in Post-Traumatic Brain Injury (TBI) Cognitive Impairment: From Pathological Changes to Therapeutic Approaches","authors":"Ningcen Li,&nbsp;Wenhui Lu,&nbsp;Limei Tang,&nbsp;Lina Zhu,&nbsp;Weibin Deng,&nbsp;Hang Liu,&nbsp;Changquan Huang,&nbsp;Jingying Jin,&nbsp;Jingjiao Zeng,&nbsp;Shitai Chen,&nbsp;Lianqi Geng,&nbsp;Xiuwu Hu,&nbsp;Liang Zhou","doi":"10.1111/cns.70568","DOIUrl":"https://doi.org/10.1111/cns.70568","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Traumatic brain injury (TBI), as a common and serious neurological disease, brings enormous physical and psychological burden to patients. Among them, cognitive impairment caused by TBI greatly affects the quality of life and social function of patients. Microglia, as key immune cells in the central nervous system, play a crucial role in the occurrence and development of cognitive impairment after TBI. This review delves into the important functions of microglia in normal physiological states and their multifaceted manifestations in post-TBI cognitive impairment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A systematic literature review was conducted using PubMed, Google Scholar, Web of Science and Scopus, with a focus on preclinical studies as well as clinical trials published in the past 20 years. The key search terms include “traumatic brain injury,” “cognitive impairment,” “microglia,” etc.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;During the acute phase of TBI injury, microglia rapidly activate, clear injury debris, and initiate repair, reducing secondary injury. At the same time, microglia undergo phenotype polarization during this stage. Some M1-type microglia can release various inflammatory factors through inflammation-related pathways, triggering inflammatory signals and leading to neuronal apoptosis and neuroinflammatory responses. M1 polarization driven persistent inflammation becomes an important factor in the chronic progression of TBI, leading to cognitive impairment. On the other hand, the phagocytic function of activated microglia also changes, which may lead to excessive phagocytosis of normal neurons and synapses, causing synaptic dysfunction and further exacerbating cognitive impairment. Meanwhile, insufficient clearance of damaged cells and debris can lead to persistent inflammation, hindering nerve repair. This review also provides a detailed introduction to potential treatment methods. This includes inhibiting the activation of microglia and the release of inflammatory factors through anti-inflammatory therapy, regulating the phenotype of microglia to promote their transformation to M2 type, promoting the normalization of microglial phagocytic function, regulating the structure and function of synapses, and using stem cell therapy to secrete neurotrophic factors to regulate microglial function. The strategy of integrating traditional Chinese and Western medicine is also a good direction.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Microglia are both the “driving force” of neu","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.70568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861581","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}