CNS Neuroscience & Therapeutics最新文献

{"title":"Transcription Factor-Based Gene Therapy Enables Functional Repair of Rat Following Chronic Ischemic Stroke","authors":"Tao Wang,&nbsp;Xu Wang,&nbsp;Shanggong Liu,&nbsp;Menglei Li,&nbsp;Kaiying Wan,&nbsp;Jiajun Zheng,&nbsp;Kai Liao,&nbsp;Jinyu Wang,&nbsp;Kaiming Zou,&nbsp;Lu Wang,&nbsp;Hao Xu,&nbsp;Wenliang Lei,&nbsp;Gong Chen,&nbsp;Wen Li","doi":"10.1111/cns.70448","DOIUrl":"https://doi.org/10.1111/cns.70448","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In vivo transcription factor (TF) -mediated gene therapy through astrocyte-to-neuron (AtN) conversion has shown therapeutic effects on rodent and non-human primate cortical ischemic injury in the subacute phase. However, in the clinic, subcortical regions including striatum as well as white matter are vulnerable regions of stroke, with millions of patients beyond subacute phase. In this study, we investigate whether TF-mediated AtN conversion therapy can be extended to treat chronic-phase ischemic stroke involving subcortical regions (e.g., striatum) and white matter, beyond cortical injuries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rat middle cerebral artery occlusion (MCAO)-like models were established to induce broad ischemic injuries including cortical and striatal regions. Then multiple rounds of TF-mediated gene therapy treatments through adeno-associated virus (AAV) system to cover the large-scaled infarct areas were conducted in the chronic phase of the stroke models. Magnetic resonance imaging (MRI), [¹⁸F] FDG-PET/CT, behavioral tests, immunohistochemistry and bulk-RNA seq were applied to evaluate the AtN conversion, tissue repair and functional recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed that administrated in the chronic phase of ischemic stroke, TF-mediated gene therapy can efficiently regenerate new neurons in both cortical and striatal regions, and promote tissue repair in both grey and white matter. Compared with single round of AAV administration, multiple rounds of treatment regenerated more neurons and led to a significant functional recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrates that TF-mediated gene therapy has a broad therapeutic time window and can be applied multiple rounds to treat severe ischemic stroke, making it an attractive therapeutic intervention in the chronic phase after stroke, when current approaches are largely ineffective.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108901","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":"Calcitriol Modulates Hippocampal Axon Guidance Through Enhanced EfnA4-Mediated PI3K/AKT Signaling in an Autism Mouse Model","authors":"Tiantian Gong,&nbsp;Ruizhen Sun,&nbsp;Jieli Bai,&nbsp;Xin Liu,&nbsp;Chenyao He,&nbsp;Qi Jiang,&nbsp;Qi Wang,&nbsp;Yubo Qi,&nbsp;Wenxin Ding,&nbsp;Jingling Shen,&nbsp;Lei Lei,&nbsp;Zhiyan Shan","doi":"10.1111/cns.70429","DOIUrl":"https://doi.org/10.1111/cns.70429","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition arising from the interplay of genetic predispositions and environmental influences. Recent studies have suggested that vitamin D (VitD) supplementation play a role in reducing the risk of ASD and alleviating some of its core symptoms. However, variations in individual responses to VitD due to biological heterogeneity have led to inconsistent clinical outcomes, and the precise molecular mechanisms through which VitD might exert its effects on ASD remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the effects of calcitriol, the biologically active form of VitD, on ASD-associated phenotypes in BTBR mice, a well-established autism model. Behavioral assessments were used to evaluate social and repetitive behaviors. Mechanistic insights were obtained through RNA sequencing, immunohistochemistry, biochemical assays, and stripe guidance assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Calcitriol supplementation significantly improved autism-like behaviors in BTBR mice, alleviating hippocampal hypoplasia and correcting axon guidance abnormalities. These effects were mediated by modulation of the EfnA4-PI3K signaling pathway in hippocampal neural progenitor cells and other brain regions, highlighting its role in neurodevelopmental processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrate that calcitriol targets axon-guidance-related signaling pathways, providing a theoretical framework and potential clinical strategy for targeted ASD interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100832","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":"ANG-Modified Liposomes Coloaded With α-Melittin and Resveratrol Induce Apoptosis and Pyroptosis in Glioblastoma Cells by Impeding Wnt/β-Catenin Signaling","authors":"Hai-Qian Zhang,&nbsp;Yan Wang,&nbsp;Xiao Geng,&nbsp;Mingxin Dong,&nbsp;Ziwei Liu,&nbsp;Chengbiao Sun,&nbsp;Kaikai Yu,&nbsp;Wenwen Xin,&nbsp;Ye Xu,&nbsp;Na Xu,&nbsp;Wensen Liu","doi":"10.1111/cns.70437","DOIUrl":"https://doi.org/10.1111/cns.70437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Main Problem</h3>\u0000 \u0000 <p>Glioblastoma (GB) is one of the most prevalent and devastating types of brain cancer for which efficient treatments are currently lacking because of limitations such as antitumor efficacy, brain delivery, tumor selectivity, and drug resistance. A promising strategy to overcome these obstacles is developing anticancer agents that can be delivered to GB tissues to inhibit tumors with low toxicity to normal brain tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed liposomes encapsulating resveratrol (RES), a polyphenolic compound, and α-melittin (α-MEL), which is composed of melittin conjugated with an amphiphilic α-helical peptide at its N-terminus. RES-, α-MEL-, and α-MEL-RES-loaded liposomes (Lips) were modified with Angiopep-2 (ANG). The effects of the above liposomes on GB cells were assessed, and the possible mechanisms were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ANG-modified α-MEL-RES-Lips treatment facilitated the passage of these agents through the blood–brain barrier (BBB), increased tumor targeting, and significantly reduced α-MEL-associated hemolysis. The combined management of α-MEL with RES impeded GB cell growth and prolonged the lifespan of GB tumor-bearing model mice. α-MEL-RES-Lips treatment triggered GB cell apoptosis and induced pyroptosis-associated protein expressions of gasdermin-D (GSDMD), gasdermin E (GSDME), cleaved caspase 3, and NLR family pyrin domain containing 3 (NLRP3), and inhibited epithelial–mesenchymal transition (EMT) by modulating the Wnt/β-catenin signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ANG-modified α-MEL-RES-Lips might be a potential nanosystem for GB therapy, and polyphenolic compounds combined with antimicrobial peptides may promote the induction of apoptosis, pyroptosis, and the apoptosis–pyroptosis switch in GB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108841","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":"Kisspeptin-10 Prevents the Development of Cerebral Aneurysms by Reducing the Expression of Egr-1","authors":"Huimin Yu,&nbsp;Minghong Xie,&nbsp;Xuancong Liufu,&nbsp;Yezi Xu,&nbsp;Lei Chen","doi":"10.1111/cns.70413","DOIUrl":"https://doi.org/10.1111/cns.70413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cerebral aneurysms (CAs) are a prevalent brain condition with poorly understood pathological features. The Kisspeptin-10 (KP-10)/G protein-coupled receptor 54 (GPR54) system is a vital neuroendocrine pathway primarily implicated in the regulation of reproductive functions and energy metabolism. This research explores the role of the KP-10/GPR54 system in CAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Serum levels of KP-10 in CA patients and animal models were assessed using commercial ELISA kits. Mice were divided into five groups: WT, GPR54^−/−, CA, CA + KP-10, and CA + GPR54^−/− + KP-10. The CA profiles were evaluated using Verhoeff-van Gieson staining. Human brain microvascular endothelial cells (HBMVECs) were stimulated with Ang II (10⁻⁷ mol/L) with or without KP-10 (50, 100 nM). Angiogenic tube formation was then assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that KP-10 levels were reduced in both CA patients and mouse models. In CA mice, Gpr54 expression in the Circle of Willis (COW) was also decreased. KP-10 reduced CA size in wild-type mice, but not in Gpr54 knockout mice. It also reduced matrix metalloproteinase-9 (MMP-9), macrophage infiltration, and vascular endothelial growth factor-A (VEGF-A) expression, effects that were absent in Gpr54 knockout mice. In vitro, KP-10 inhibited Ang II-induced proliferation, angiogenic tube formation, and VEGF-A expression in HBMVECs by reducing early growth response-1 (Egr-1). These effects were abolished when Gpr54 was knocked down, indicating that KP-10's action is dependent on Gpr54.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows that KP-10 binding to Gpr54 inhibits Egr-1 expression, thereby suppressing MMP-9 and VEGF-A, reducing macrophage infiltration and angiogenesis, and preventing cerebral aneurysm development. Thus, the KP-10/Gpr54 system is a key therapeutic target for the treatment of cerebral aneurysms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085223","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":"Comparative Efficacy and Safety of Extended Versus Standard Interval Dosing of Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients: A Multicenter Analysis","authors":"Meral Seferoğlu,&nbsp;Abdulkadir Tunç,&nbsp;Ali Özhan Sıvacı,&nbsp;Bilge Piri Çınar,&nbsp;Sena Destan Bünül,&nbsp;Özlem Ethemoğlu,&nbsp;Ülgen Yalaz Tekan,&nbsp;Mehmet Fatih Yetkin","doi":"10.1111/cns.70445","DOIUrl":"https://doi.org/10.1111/cns.70445","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extended interval dosing (EID) of natalizumab (NTZ) every 6 weeks may reduce adverse events while maintaining efficacy. This study compared the effectiveness and safety of EID versus standard interval dosing (SID) in relapsing–remitting multiple sclerosis (RRMS) patients, focusing on treatment adherence and its impact on clinical and radiological outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study involved 80 patients with RRMS from seven clinics: 52 received SID (300 mg every 4 weeks), and 28 received EID (300 mg every 6 weeks). Clinical and radiological disease activity, treatment adherence, and adverse events were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The SID and EID groups differed significantly in sex distribution (78.8% female in SID vs. 46.4% in EID, <i>p</i> = 0.007), but median age was similar (32 vs. 36 years, <i>p</i> = 0.209). Clinical and radiological worsening rates were similar between the groups, with no significant differences (combined worsening: 9.6% in the SID group vs. 17.9% in the EID group, <i>p</i> = 0.308; radiological worsening: 5.8% in the SID group vs. 7.1% in the EID group, <i>p</i> = 1.00; clinical worsening: 9.6% in the SID group vs. 10.7% in the EID group, <i>p</i> = 1.00). Adherence rates were comparable across both dosing regimens, and no significant differences were observed in terms of treatment discontinuation. No progressive multifocal leukoencephalopathy cases were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both SID and EID provide comparable efficacy and safety profiles, with similar adherence rates. Despite the observed sex distribution imbalance, additional analyses confirmed no significant sex- or group-related differences in baseline disability or clinical worsening, strengthening the interpretation that EID preserves efficacy. Findings should still be interpreted with caution due to the study's retrospective nature and limited sample size.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085203","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":"ALOX15-Mediated Neuron Ferroptosis Was Involved in Diabetic Peripheral Neuropathic Pain","authors":"Zhiye Feng,&nbsp;Fuye Li,&nbsp;Zhiqiang Lin,&nbsp;Jian Liu,&nbsp;Xi Chen,&nbsp;Wenxu Yan,&nbsp;Zhongjie Liu","doi":"10.1111/cns.70440","DOIUrl":"https://doi.org/10.1111/cns.70440","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic peripheral neuropathic pain (DPNP) is one of the most common complications in diabetic patients. Current treatment strategies primarily focus on blood glucose control and pain relief, but they often yield limited effects. Ferroptosis, a regulated form of cell death driven by lipid peroxidation and iron imbalance, plays a crucial role in various diseases, including neuropathic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we employed a combined bioinformatics and machine learning approach to identify genes most strongly associated with DPNP and ferroptosis. Subsequently, we established a DPNP mouse model via streptozotocin (STZ) injection and a high-glucose-induced SH-SY5Y cell injury model. ALOX15 was knocked down in the in vitro model using siRNA transfection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bioinformatics analysis identified ALOX15 as a hub gene linking DPNP and ferroptosis. In both in vivo and in vitro DPNP models, ALOX15 expression was significantly upregulated and correlated with ferroptosis biomarkers. Knockdown of ALOX15 in the cellular model mitigated high-glucose-induced ferroptosis, reduced lipid peroxidation and free iron ion accumulation, and restored cell viability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, ALOX15 contributes to the onset and progression of DPNP by promoting ferroptosis, and its knockdown effectively suppresses ferroptosis, providing a novel target and strategy for DPNP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085224","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":"Therapeutic Potential of Anti-Diabetes Drugs and Anti-Dyslipidemia Drugs to Mitigate Head and Neck Cancer Risk in Metabolic Syndrome","authors":"Sujung Yeom,&nbsp;Dong Hoon Lee,&nbsp;Juhyun Song","doi":"10.1111/cns.70446","DOIUrl":"https://doi.org/10.1111/cns.70446","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Head and neck cancer (HNC) encompasses a heterogeneous group of malignancies originating in the oral cavity, pharynx, nasopharynx, larynx, paranasal sinuses, and salivary glands. Accumulating evidence indicates that metabolic syndrome (MetS) characterized by a constellation of conditions including central adiposity, hyperglycemia, dyslipidemia, hypertension, and insulin resistance, may significantly influence cancer pathogenesis and progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MetS has been epidemiologically linked to elevated risk for multiple malignancies through various metabolic mechanisms involving chronic systemic inflammation, insulin resistance, and dysregulated lipid metabolism. Especially in HNC, recent studies demonstrated that MetS and metabolic imbalance conditions may contribute to carcinogenesis, disease progression, and clinical outcomes, but the exact mechanisms behind the association between excess fat accumulation and HNC risk remain unclear. Considering previous studies, pharmacological agents targeting metabolic pathways, including biguanides (metformin), thiazolidinediones, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and HMG-CoA reductase inhibitors (statins) are being investigated for potential repurposing in cancer prevention and adjuvant therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Here, we summarize the latest evidence on the relationship between MetS and HNC, highlighting the therapeutic potential of anti-diabetes drugs and anti-dyslipidemia drugs in ameliorating various pathological problems in HNC patients with MetS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Dexmedetomidine With Postoperative Depressive Symptoms in Older Surgical Patients: A Prospective Multicenter Study","authors":"Xinyu Hao,&nbsp;Zhuoning Zhang,&nbsp;Lujia Yang,&nbsp;Yongxin Guo,&nbsp;Fuyang Cao,&nbsp;Jiangbei Cao,&nbsp;Yanhong Liu,&nbsp;Jingsheng Lou,&nbsp;Ziyao Xu,&nbsp;Yulong Cui,&nbsp;Yunxiao Bai,&nbsp;Xiaoping Gu,&nbsp;Difen Wang,&nbsp;Qianyu Cui,&nbsp;Zhikang Zhou,&nbsp;Hao Shen,&nbsp;Jingjia Sun,&nbsp;Weidong Mi,&nbsp;Li Tong","doi":"10.1111/cns.70407","DOIUrl":"https://doi.org/10.1111/cns.70407","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;Neuropsychiatric symptoms significantly impact surgical recovery, quality of life, and long-term survival. To investigate the association between intraoperative dexmedetomidine administration and the incidence of postoperative depressive symptoms in noncardiac surgical patients.&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;A multicenter prospective observational study of older surgical patients over 65 years of age from April 2020 to April 2022. The primary outcome was the incidence of postoperative 7-day depressive symptoms. Secondary outcomes were the incidence of postoperative 7-day anxiety symptoms, sleep disturbance, and delirium. A logistic regression model based on the random effect was used to determine the association between dexmedetomidine administration and the outcomes. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were employed to address data imbalance. Subgroup analyses based on specific populations were performed to explore the relationship between dexmedetomidine and depressive symptoms.&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;Of 5591 patients, 20.5% (1148) received intraoperative dexmedetomidine. The incidence of postoperative 7-day depressive symptoms was significantly lower in the dexmedetomidine group compared to the nondexmedetomidine group (unadjusted: 7.6% vs. 26.7%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; PSM: 7.9% vs. 29.0%, IPTW: 8.7% vs. 25.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Dexmedetomidine was significantly associated with the remission of postoperative 7-day depressive symptoms (adjusted random-effect model: risk ratio [RR] 0.104, 95% CI, 0.080–0.140, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; PSM: RR 0.311, 95% CI, 0.242–0.415, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; IPTW: RR 0.297, 95% CI, 0.253–0.343, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Additionally, dexmedetomidine demonstrated protective effects against postoperative anxiety symptoms, sleep disturbance, and delirium. In age, gender, cumulative comorbidity, frailty, ASA physical status, and inhaled anesthetic subgroups, we also found that dexmedetomidine was associated with a reduction in postoperative depressive symptoms in older noncardiac patients.&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;Intraoperative dexmedetomidine administration was associated with a reduction in postoperative 7-day depressive symptoms, anxiety symptoms, sleep disturbances, and delirium in older patients undergoing noncardiac surgery.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Trial Registration&lt;/h3&gt;\u0000 \u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085222","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":"Auricular Transcutaneous Vagus Nerve Stimulation Enhances Post-Stroke Neurological and Cognitive Recovery in Mice by Suppressing Ferroptosis Through α7 Nicotinic Acetylcholine Receptor Activation","authors":"Hongyan Gong,&nbsp;Fang Zheng,&nbsp;Bochao Niu,&nbsp;Bin Wang,&nbsp;Lin Xu,&nbsp;Yunchao Yang,&nbsp;Jiahan Wang,&nbsp;Xiaopeng Tang,&nbsp;Yanlin Bi","doi":"10.1111/cns.70439","DOIUrl":"https://doi.org/10.1111/cns.70439","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ferroptosis plays a critical role in stroke pathophysiology, yet its dynamics during recovery remain unclear. This study aimed to investigate the evolution of ferroptosis throughout post-stroke recovery and evaluate auricular transcutaneous vagus nerve stimulation (atVNS) as a therapeutic intervention, focusing on the involvement of α7 nicotinic acetylcholine receptor (α7nAChR)-mediated mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a middle cerebral artery occlusion (MCAO) mouse model, we examined ferroptosis-related protein expression (GPX4, ACSL4, TfR) and iron levels across acute to chronic recovery phases. The therapeutic effects of atVNS were evaluated through the assessment of ferroptosis markers, neurogenesis, angiogenesis, cognitive function, and neuroinflammation. α7nAChR knockout mice were used to investigate the receptor's role in atVNS-mediated recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed sustained alterations in ferroptosis markers and iron levels throughout post-stroke recovery. atVNS treatment reduced ferroptosis progression by modulating GPX4 and ACSL4 expression, enhanced neurogenesis and angiogenesis, improved cognitive recovery, and reduced neuroinflammation. These beneficial effects were absent in α7nAChR knockout mice, while atVNS increased neuronal α7nAChR expression in wild-type mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals the persistent involvement of ferroptosis in stroke recovery and demonstrates that atVNS provides comprehensive neuroprotection through α7nAChR-dependent mechanisms. These findings establish atVNS as a promising noninvasive therapeutic approach for stroke recovery and highlight α7nAChR signaling as a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074336","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":"Diffusion Tensor Imaging Along the Perivascular Space Is a Promising Imaging Method in Parkinson's Disease: A Systematic Review and Meta-Analysis Study","authors":"Kiarash Shirbandi,&nbsp;Mostafa Jafari,&nbsp;Fatemeh Mazaheri,&nbsp;Marziyeh Tahmasbi","doi":"10.1111/cns.70434","DOIUrl":"https://doi.org/10.1111/cns.70434","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder that primarily affects motor functions. Recently, a diffusion tensor imaging technique called DTI along the perivascular space (DTI-ALPS) has gained attention as a noninvasive biomarker for glymphatic function. This systematic review and meta-analysis aimed to evaluate the potential and implications of the DTI-ALPS index for diagnosing PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study followed the PRISMA 2020 statement. Eligible cohort and cross-sectional studies measured the ALPS index in PD patients versus non-PD participants. Web of Science, Medline, Scopus, Embase, Cochrane, PROSPERO, and ICTRP databases were explored until November 14, 2024. Two researchers independently screened studies, extracted data, and assessed the risk of bias using the Newcastle–Ottawa Scale (NOS). The meta-analysis used a random effects model (REM), assessing heterogeneity (<i>I</i>², Q-test) and publication bias (Egger's test, trim&amp;fill plot). The certainty of the evidence was evaluated using the GRADE approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This meta-analysis of 11 studies, involving 1462 patients (855 PD, 607 non-PD of both genders), yielded significant findings. The overall ALPS index differed substantially between PD and non-PD groups (SMD: −0.61, 95% CI: −0.72, −0.50, <i>p</i> &lt; 0.001). Additionally, a significant negative correlation emerged between the ALPS index and Unified PD Rating Scale III (UPDRS III) (r = −0.40, (95% CI: −0.59, −0.18, <i>I</i>²: 89.81, <i>p</i> &lt; 0.001)), indicating glymphatic dysfunction's impact on cognitive decline. However, a weak and statistically non-significant correlation was observed between the ALPS index and Montreal Cognitive Assessment (MoCA) (<i>r</i> = 0.24, 95% CI: −0.32 to 0.68), with high heterogeneity across studies (<i>I</i>² = 87.37, <i>p</i> &lt; 0.001 for heterogeneity). Publication bias risk was low for the overall ALPS index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the potential of DTI-ALPS as a noninvasive biomarker for PD diagnosis and progression monitoring. Further studies are warranted to explore its applicability in differentiating PD from other neurodegenerative disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074337","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}