CNS Neuroscience & Therapeutics最新文献

{"title":"MicroRNA-21a-5p Promotes Cerebral Angiogenesis in Transient Ischemic Attack by Targeting RBMS3 and Subsequently Modulating the TGFBR1/SMAD2/3 Pathway","authors":"Jiahui Wang,&nbsp;Yanyan Li,&nbsp;Jingyi Wang,&nbsp;Shiling Chen,&nbsp;Luwei Nie,&nbsp;Xuan Wu,&nbsp;Jiarui Li,&nbsp;Ping Zhang,&nbsp;Zhouping Tang","doi":"10.1111/cns.70573","DOIUrl":"https://doi.org/10.1111/cns.70573","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Transient ischemic attack (TIA) serves as a crucial precursor to a potential stroke. Angiogenesis is essential for the renovation of the damaged brain after TIA. This study aimed to elucidate the role of miRNA-21a-5p in angiogenesis following TIA and unravel the underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo and in vitro TIA models were established using the modified suture middle cerebral artery occlusion and oxygen–glucose deprivation/reoxygenation methods. Differentially expressed miRNAs in the TIA group versus the control group were identified using small RNA sequencing. The putative target genes of miRNA-21a-5p were predicted via bioinformatics analysis and validated using a dual luciferase reporter gene assay. TIA models were then treated with miRNA-21a-5p antagomir/agomir or/and an adeno-associated virus interfering with the target gene to assess the effects of miRNA-21a-5p and the identified target gene on angiogenesis after TIA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MiRNA-21a-5p was the miRNA with the most significant changes after TIA. RBMS3 was identified as a target gene for miRNA-21a-5p. Downregulation of miRNA-21a-5p expression reduced angiogenesis in animal and cellular models of TIA, and miRNA-21a-5p upregulation had a completely opposite effect. RBMS3 suppression reversed miRNA-21a-5p knockdown-mediated inhibition of angiogenesis in TIA models. Moreover, the TGFBR1/SMAD2/3 pathway was found to be downstream for miRNA<b>-</b>21a-5p/RBMS3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MiRNA-21a-5p conferred neuroprotective effects against TIA by enhancing angiogenesis through the RBMS3/TGFBR1/SMAD2/3 pathway.</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.70573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861589","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":"Optimal Stimulation Sites and Connectomes for GPi and STN-DBS in Cervical Dystonia","authors":"Tao Xue,&nbsp;Youjia Qiu,&nbsp;Wei Tian,&nbsp;Hutao Xie,&nbsp;Shiying Fan,&nbsp;Houyou Fan,&nbsp;Minjia Xie,&nbsp;Ming Ye,&nbsp;Zhong Wang,&nbsp;Tongbo Ning,&nbsp;Chunlei Han,&nbsp;Hua Zhang,&nbsp;Anchao Yang,&nbsp;Lin Sang,&nbsp;Jurgen Germann,&nbsp;Alexandre Boutet,&nbsp;Joseph Tam,&nbsp;Andres M. Lozano,&nbsp;Fangang Meng,&nbsp;Yutong Bai,&nbsp;Jianguo Zhang","doi":"10.1111/cns.70561","DOIUrl":"https://doi.org/10.1111/cns.70561","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To map optimal stimulation targets (sweet spots) and neural networks for globus pallidus internus (GPi)- and subthalamic nucleus (STN)-deep brain stimulation (DBS) in cervical dystonia (CD), and compare their structural/functional connectivity profiles and predictive validity for clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective analysis of 76 stimulation settings from 38 CD patients across four centers. Volume of tissue activated was reconstructed; connectivity-based sweet spots were identified. Structural/functional connectivity models were developed using normative connectomes and validated externally. Clinical outcomes were assessed using validated scales.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Optimal targets localized to the posterior ventral medial GPi and dorsolateral STN. The ideal probabilistic stimulation maps of STN-DBS exhibited predictive clinical improvement. Both targets showed beneficial connections to the motor cortex, with GPi-DBS negatively connected to the occipital lobe and STN-DBS positively connected to the premotor cortex and cerebellum. Functional connectivity patterns further highlighted shared and distinct regions linked to CD symptoms. Moreover, the structural and functional connectivity models predicted postoperative improvement through internal and external validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GPi- and STN-DBS engage distinct but overlapping networks in CD. Connectivity-based models robustly predict clinical improvement, offering tools for personalized targeting and programming. These findings clarify network mechanisms of DBS in dystonia and advance precision neuromodulation strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861809","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":"Hypothalamic Orexin Projections to the Hippocampal CA1 Region Alleviate Cognitive and Synaptic Plasticity Impairments Induced by Blue Light Exposure","authors":"Zhe Feng,&nbsp;Qingqing Li,&nbsp;Zhenquan He,&nbsp;Baocong Yu,&nbsp;Ting Mi,&nbsp;Jiandong Niu,&nbsp;Yuhong He,&nbsp;Qi Li,&nbsp;Xi Chen,&nbsp;Jianguo Niu,&nbsp;Dan Ding","doi":"10.1111/cns.70551","DOIUrl":"https://doi.org/10.1111/cns.70551","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Exposure to blue light emitted from electronic devices has been shown to impair cognitive performance; however, the mechanisms underlying these deleterious effects remain poorly understood. Orexin neurons in the hypothalamus, which play a key role in modulating cognitive processes and synaptic plasticity, project directly to the hippocampus, a brain region critical for learning and memory. Therefore, our study provides novel insights into the neural mechanisms underlying blue light-related cognitive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>In this study, we evaluated cognitive impairments in mice subjected to 21 days of blue light exposure using open-field, novel object recognition, and Morris water maze tests. Electrophysiological recordings and Golgi staining revealed that synaptic plasticity was significantly impaired in blue light-exposed mice. The results of biochemical experiments indicated that the expression of Orexin-A, along with the synaptic plasticity-related factors PSD-95 and SYN-1, was downregulated at both the protein and gene levels in the hippocampus of mice following blue light exposure. Furthermore, retrograde tracing combined with immunofluorescence staining showed that hypothalamic orexin neurons projected to the hippocampus, and that CTb-labeled orexin neurons were significantly activated in the hypothalamus (c-FOS⁺) of blue light-exposed mice. Notably, we found that chemogenetic activation of the hypothalamic orexin–hippocampus neural pathway significantly alleviated cognitive functions, accompanied by enhanced expression of Orexin-A, PSD-95, and SYN-1 at both the protein and gene levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that the hypothalamic orexin projections to the hippocampal CA1 region alleviate cognitive and synaptic plasticity impairments induced by blue light exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861873","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":"Levodopa and Plant-Derived Bioactive Compounds in Parkinson's Disease: Mechanisms, Efficacy, and Future Perspectives","authors":"Emre Aktaş,&nbsp;Haşmet Ayhan Hanağası,&nbsp;Nehir Özdemir Özgentürk","doi":"10.1111/cns.70540","DOIUrl":"https://doi.org/10.1111/cns.70540","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, resulting in dopamine deficiency and motor dysfunction. While levodopa (L-DOPA) remains the gold standard for symptomatic treatment, its long-term administration is associated with complications such as motor fluctuations, dyskinesia, and oxidative stress. Given these limitations, interest has grown in plant-derived bioactive compounds for their potential neuroprotective and disease-modifying effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature review was conducted across PubMed, Scopus, Google Scholar, and Web of Science, focusing on peer-reviewed studies published between 2023 and March 2025. The inclusion criteria targeted in vitro and in vivo preclinical studies as well as clinical trials that directly compared levodopa with plant-derived compounds in the context of PD. Key search terms included “Parkinson's disease,” “levodopa,” “phytochemicals,” and “plant-based neuroprotection”.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recent studies have highlighted several classes of plant-based compounds—including polyphenols (resveratrol, curcumin, EGCG), flavonoids (quercetin, apigenin, naringenin), alkaloids (berberine, caffeine, L-DOPA derived from <i>Mucuna pruriens</i>), and terpenoids (ginkgolide B, celastrol)—as potential neuroprotective agents. These compounds exert multiple actions, such as reducing oxidative stress, blocking neuroinflammation, preventing α-synuclein aggregation, and protecting mitochondria. Although levodopa effectively addresses motor symptoms, these phytochemicals may complement conventional therapy by targeting underlying disease processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although levodopa is indispensable for the symptomatic management of PD, emerging evidence supports the integration of plant-derived bioactive compounds as adjunct therapies with disease-modifying potential. Future research should prioritize improving bioavailability, developing standardized formulations, and conducting long-term clinical trials to evaluate the translational applicability of these natural agents in Parkinson's disease therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833087","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":"Endothelial Glycocalyx in Cerebral Infarction After Endovascular Treatment in Patients With Intracranial Artery Stenosis","authors":"Fangfang Zhao,&nbsp;Tao Wang,&nbsp;Jichang Luo,&nbsp;Haoyuan Gao,&nbsp;Yangmin Zheng,&nbsp;Rongliang Wang,&nbsp;Junfen Fan,&nbsp;Haiping Zhao,&nbsp;Ziping Han,&nbsp;Yumin Luo,&nbsp;Liqun Jiao","doi":"10.1111/cns.70545","DOIUrl":"https://doi.org/10.1111/cns.70545","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To examine whether plasma glycocalyx levels in patients with severe intracranial arterial stenosis (ICAS) are associated with the prediction of new cerebral infarctions following endovascular treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>105 patients with ICAS who underwent endovascular treatment were enrolled from September 2020 to June 2021. Plasma glycocalyx components were detected. The condition of the cerebral artery was obtained by high-resolution nuclear magnetic resonance, and risk factors for new cerebral infarction postendovascular treatment in patients with ICAS were analyzed using both univariate and multivariate analyses. The results were presented in a nomogram risk model and evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The plasma glycocalyx in patients with ICAS exhibited significant differences compared to healthy individuals (<i>p</i> &lt; 0.05). Multivariate analysis revealed eccentricity (OR = 3.599, 95% CI: 1.168–12.478, <i>p</i> = 0.032) and hyaluronic acid (OR = 5.542, 95% CI: 1.545–23.573, <i>p</i> = 0.013) as risk factors (<i>p</i> &lt; 0.05). The risk model encompassing eccentricity, Remodeling index, blood glucose, hyaluronic acid (HA), and age was presented as a Nomogram, with a C-index of 0.810 (95% CI, 0.729–0.890). To further analyze the risk factors affecting HA plasma concentration, the multivariate analysis showed that fibrinogen and hemoglobin A1c (HbA1C) significantly affected changes in HA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found that HA is a critical factor in predicting adverse events of cerebral infarction after endovascular treatment in patients with ICAS. Additionally, HbA1C and fibrinogen were identified as factors influencing HA changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov Identifier: NCT01994161</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833086","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":"Identifying Risk Factors and Constructing Predictive Models for Wearing-Off and Dyskinesia in Chinese Patients With Parkinson's Disease on Long-Term Levodopa Therapy","authors":"Jing Zhao,&nbsp;Yunlei Gao,&nbsp;Chong Shi,&nbsp;Jia Chen,&nbsp;Yanhong Wang,&nbsp;Jiaqi Chen,&nbsp;Shaochen Ma,&nbsp;Peifu Wang,&nbsp;Jilai Li,&nbsp;Jichen Du,&nbsp;Zhirong Wan","doi":"10.1111/cns.70544","DOIUrl":"https://doi.org/10.1111/cns.70544","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to investigate the incidence and risk factors of motor complications including wearing-off (WO) and dyskinesia during long-term levodopa (LD) therapy in Chinese patients with Parkinson's disease (PD), and develop corresponding predictive models, thereby providing a basis for personalized treatment strategies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This cross-sectional study included 208 consecutive PD patients who were recruited. The presence of WO and dyskinesia was assessed by a 9-item wearing-off questionnaire and the Unified Parkinson's Disease Rating Scale part IV. Univariate and multivariate logistic regression analyses were used to predict the risk factors of WO and dyskinesia. Predictive models for WO and dyskinesia were then constructed, and their diagnostic performance was evaluated using the area under the curve (AUC).&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;The overall prevalence rate of motor complications was 46.2% (96/208), with a prevalence of 45.7% (95/208) for WO, 22.1% (46/208) for dyskinesia, and 21.6% (45/208) for the simultaneous occurrence of WO and dyskinesia. Younger age at onset (OR 0.92, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), higher levodopa-equivalent daily dose (LEDD) (OR 1.00, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and higher Hoehn-Yahr stage (OR 3.41, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) were independent risk factors for WO. A predictive model for WO constructed using these three variables demonstrated high diagnostic efficacy with an AUC of 0.887 (95% CI 0.842–0.932), a sensitivity of 84%, and a specificity of 83%. The independent risk factors for dyskinesia included younger age at onset (OR 0.94, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), akinetic-rigid type (OR 2.42, &lt;i&gt;p&lt;/i&gt; = 0.034), and higher LEDD (OR 1.01, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). A predictive model for dyskinesia constructed using these three variables yielded an AUC value of 0.829 (95% CI 0.767–0.897), with a sensitivity of 67% and a specificity of 89%. The two models were both well calibrated and had a high net clinical benefit.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findings suggest that the prevalence of motor complications during long-term LD treatment is relatively high among PD patients in China, with WO occurring more commonly than dyskinesia. Younger age at PD onset, higher LEDD, more severe disease, and akinetic-rigid subtype are key predictors of motor complications. The predictive models developed in this study could serve as a potential tool to assist clinicians in identifying patients at higher risk for WO and dyskinesia, and may support per","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811109","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":"Gastrodin Attenuates Cerebral Ischemia–Reperfusion Injury by Enhancing Mitochondrial Fusion and Activating the AMPK-OPA1 Signaling Pathway","authors":"Zihan Liu,&nbsp;Zeyu Han,&nbsp;Wenshuai Bao,&nbsp;Yihan Guo,&nbsp;Yuan Yuan,&nbsp;Jianming Cheng,&nbsp;Jie Zhang,&nbsp;Yang Hu","doi":"10.1111/cns.70559","DOIUrl":"https://doi.org/10.1111/cns.70559","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral ischemia–reperfusion (I/R) injury is a critical pathological process in stroke, characterized by disrupted energy metabolism, inflammatory responses, and mitochondrial dysfunction. Targeting mitochondrial dynamics presents promising strategies for alleviating brain injury. This study investigates the role and mechanism of Gastrodin (Gas) in regulating mitochondrial dynamics and mitigating cerebral I/R injury via activation of the AMPK-OPA1 signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An in vitro oxygen–glucose deprivation/reperfusion (OGD/R) model and an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) model were used to assess the effects of Gas on inflammation, mitochondrial function, and energy metabolism. Immunofluorescence, western blotting (WB), reverse-transcription PCR (RT-PCR), JC-1 staining, and molecular docking techniques were employed for analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gas activated the AMPK-OPA1 signaling pathway, promoting mitochondrial fusion, restoring membrane potential, enhancing ATP production, and rebalancing NAD⁺/NADH levels. Additionally, Gas significantly suppressed I/R-induced inflammatory responses, reduced neuronal damage, and decreased infarct volume. Notably, its protective effects on mitochondrial fusion and neuroprotection were abolished under AMPK silencing, highlighting the critical role of the AMPK-OPA1 pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gas alleviates cerebral I/R injury by regulating mitochondrial dynamics via the AMPK-OPA1 signaling pathway. These findings provide a theoretical basis for the therapeutic application of Gas in stroke and offer new insights into mitochondrial-targeted treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815072","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":"Safety and Efficacy of a Neonatal Fc Receptor Antagonist in Patients With Anti-NMDAR Encephalitis","authors":"Zhihong Bian,&nbsp;Han Cai,&nbsp;Haotian Wu,&nbsp;Ping Liu,&nbsp;Yanfang Zuo,&nbsp;Fuhua Peng,&nbsp;Wei Qiu,&nbsp;Zhengqi Lu,&nbsp;Bingjun Zhang","doi":"10.1111/cns.70534","DOIUrl":"https://doi.org/10.1111/cns.70534","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This retrospective study investigates the safety and effectiveness of efgartigimod in improving clinical outcomes for patients with anti-NMDAR encephalitis in a real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 26 patients diagnosed with anti-NMDAR encephalitis at the Third Affiliated Hospital of Sun Yat-sen University between October 2022 and June 2024. The patients were divided into two groups: 13 received efgartigimod treatment, while 13 did not. Clinical outcomes were assessed using the modified Rankin Scale (mRS), the Clinical Assessment Scale in Autoimmune Encephalitis (CASE), and clinical symptoms, along with an analysis of treatment-emergent adverse events (TEAEs), cerebrospinal fluid (CSF) antibody titers, and blood serum IgG levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Efgartigimod treatment was associated with significant clinical improvement, as indicated by greater reductions in mRS and CASE scores at discharge and follow-up compared to the control group. At follow-up, 84.6% of patients in the efgartigimod group achieved an mRS score of ≤ 2, compared to 46.2% in the control group. Additionally, patients receiving Efgartigimod exhibited a notable reduction in CSF anti-NMDAR antibody titers and serum IgG levels. The most common TEAEs were mild to moderate infections, with no significant safety concerns identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this exploratory study, efgartigimod demonstrated a favorable safety profile for patients with anti-NMDAR encephalitis and appeared to facilitate the recovery of clinical symptoms and neurological function. However, further prospective randomized studies with larger patient cohorts are necessary to confirm the safety and efficacy of efgartigimod.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811095","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":"Trimethylamine N-Oxide Mitigates Perioperative Neurocognitive Disorders via ANXA1 Nuclear Translocation and M2 Microglial Polarization in the Hippocampus","authors":"Mengxin Que,&nbsp;Li Luo,&nbsp;Xuan Wang,&nbsp;Shiyong Li,&nbsp;Qian Xia,&nbsp;Xing Li,&nbsp;Ailin Luo,&nbsp;Gaofeng Zhan","doi":"10.1111/cns.70558","DOIUrl":"https://doi.org/10.1111/cns.70558","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study investigates whether trimethylamine N-oxide (TMAO) mitigates perioperative neurocognitive disorders (PND) by modulating Annexin A1 (ANXA1) and microglial polarization, thereby reducing neuroinflammation in the hippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A murine PND model was established via tibial fracture surgery under sevoflurane anesthesia. Mice were pretreated with TMAO (1.2, 12, or 120 mg/kg) for 21 days. Cognitive function was assessed using Y-maze and fear conditioning tests. Hippocampal ANXA1 expression, microglial polarization (M1/M2 phenotypes), and cytokine levels (TNF-α, IL-1β, TGF-β) were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TMAO administration (12 mg/kg) significantly improved cognitive performance. Mechanistically, TMAO upregulated ANXA1 expression, facilitating its nuclear translocation in microglia and shifting their polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. This transition consequently suppressed pro-inflammatory cytokines (TNF-α and IL-1β) while elevating TGF-β. Additionally, TMAO attenuated microglial activation and associated neuroinflammatory morphological alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Physiological concentrations of TMAO confer neuroprotection by augmenting ANXA1-mediated resolution of neuroinflammation, supporting its therapeutic potential for preventing PND.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811072","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":"Sex Differences in Functional Gradients and Dynamic Functional Connectivity in Preschool-Aged Children With ASD","authors":"Guangrong Wu,&nbsp;Linfeng Song,&nbsp;Guomin Zhang,&nbsp;Yuanyuan Xu,&nbsp;Jie Fang,&nbsp;Siyan Xiong,&nbsp;Wei Yang,&nbsp;Lin Jiang","doi":"10.1111/cns.70562","DOIUrl":"https://doi.org/10.1111/cns.70562","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prevalence of autism spectrum disorder (ASD) is significantly higher in males than in females; although the underlying etiology remains unclear. This study aimed to investigate the multi-scale reorganization of brain networks in preschool-aged boys with ASD and their impact on clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 54 children with ASD (40 boys and 14 girls) and 44 typically developing (TD) children (28 boys and 16 girls), aged between 2 and 6 years, were recruited for this study. Functional gradient analysis and dynamic functional connectivity were used to examine differences in the hierarchical organization of brain functional networks between preschool-aged boys and girls with ASD compared to their corresponding typically developing peers. Subsequently, multiple machine learning models were applied to evaluate the classification performance of the identified abnormal features in distinguishing ASD from TD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that the ASD group exhibited functional gradient abnormalities in multiple brain networks: (1) In boys with ASD, primary gradient abnormalities were identified in the dorsal attention network, limbic network, ventral attention network, and default mode network (DMN), whereas in girls with ASD, primary gradient abnormalities were only found in the DMN; (2) Secondary gradient abnormalities in boys with ASD were found in the sensorimotor network (SMN), ventral attention network, and DMN, while in girls with ASD, secondary gradient abnormalities were restricted to the DMN and SMN; (3) Third gradient abnormalities in boys with ASD were observed only in the visual network, whereas in girls with ASD, abnormalities were present in the limbic network, SMN, and visual network; (4) Enhanced dynamic functional connectivity was detected in boys with ASD only in state 1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preschool-aged boys and girls with ASD exhibit significant sex differences in functional gradients and dynamic functional connectivity, underscoring the complexity and heterogeneity of ASD. These findings provide a novel theoretical framework for understanding the neuroimaging mechanisms underlying ASD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811071","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}