CNS Neuroscience & Therapeutics最新文献

{"title":"Elucidating the Neuroprotective Mechanisms of G-3702 in Ischemic Stroke via Integrated Metabolomics and Computational Approaches","authors":"Cong Wang, Fang Zhang, Qi Zheng, Junsong Wang","doi":"10.1111/cns.70352","DOIUrl":"https://doi.org/10.1111/cns.70352","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ischemic stroke (IS) remains a leading cause of disability worldwide, necessitating the development of more effective treatments. While DL-3-n-butylphthalide (NBP) has shown promise in treating IS, its clinical application is limited by hepatotoxicity. G-3702, a structural analog of NBP, has emerged as a potential alternative with reduced hepatotoxicity and proposed pro-angiogenic effects. However, the precise mechanisms underlying G-3702's therapeutic effects in IS remain unclear, hindering its optimization and the identification of novel therapeutic targets. This gap in understanding is particularly significant given the potential of pro-angiogenic treatments to address ischemia-induced vascular damage and improve long-term recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we employed an integrated approach combining metabolomics, transcriptomics, and machine learning to elucidate G-3702's mechanisms of action in a photothrombotic stroke mouse model. Untargeted metabolomics and pathway analysis explored G-3702's metabolic impacts, while network pharmacology and machine learning algorithms refined key therapeutic target identification. We validated computational insights through immunofluorescence and qPCR experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results demonstrated that G-3702 significantly improved neurological outcomes and reduced cerebral cortex necrosis in IS mice. Metabolomics implicated the Avb3 integrin pathway in G-3702's pro-angiogenic effects, while computational analyses highlighted the PI3K-Akt and HIF-1α pathways as central to this action. Machine learning algorithms prioritized potential biomarkers and targets, including BDNF, FGF2, ITGAV, ITGB3, SRC, and RHOA. Immunofluorescence confirmed enhanced angiogenesis, and qPCR demonstrated increased expression of these angiogenesis-related genes following G-3702 treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that G-3702 promotes angiogenesis in the ischemic brain area primarily via the Avb3 integrin pathway, offering a mechanistic explanation for its therapeutic effects in IS. By elucidating G-3702's mode of action, this study not only enhances its clinical potential but also contributes to the broader field of stroke treatment by identifying novel therapeutic targets. Our integrated approach to mechanism elucidation advances the understanding of pro-angiogenic treatments for stroke and may serve as a model for future drug development efforts in IS and other complex neurological disord","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861920","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":"Chronic Intermittent Hypoxia-Induced Neural Injury: Pathophysiology, Neurodegenerative Implications, and Therapeutic Insights","authors":"Nan-Nan Jia,&nbsp;Meng-Fan Yao,&nbsp;Chun-Xue Zhu,&nbsp;Mei-Juan He,&nbsp;Hai-Feng Zhu,&nbsp;Zun-Yu Chen,&nbsp;Han-Peng Huang,&nbsp;Chen Qiao","doi":"10.1111/cns.70384","DOIUrl":"https://doi.org/10.1111/cns.70384","url":null,"abstract":"<p>Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep-related respiratory disorder that poses a global threat to human health. Chronic intermittent hypoxia (CIH) is its main pathological feature. With the advancements in medical research, the study of CIH-induced neural injury has gained increasing attention. Studies have shown that CIH can lead to or aggravate neuroinflammation and apoptosis by increasing blood–brain barrier (BBB) permeability, promoting oxidative stress, activating glial cells, and triggering multiple signaling pathways, ultimately resulting in neural injury. These processes contribute to the development of Alzheimer's disease, Parkinson's disease, and stroke. This review aims to summarize the progress in CIH-induced neural injury and explore various underlying mechanisms, with the goal of providing new insights for the development of therapeutic interventions targeting CIH-related neural damage.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856739","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":"Effect of Brain Computer Interface Training on Frontoparietal Network Function for Young People: A Functional Near-Infrared Spectroscopy Study","authors":"Yulan Xu,&nbsp;Yuan Lanhui Li,&nbsp;Guancong Yu,&nbsp;Zitong Ou,&nbsp;Shantong Yao,&nbsp;Yawen Li,&nbsp;Yuhong Huang,&nbsp;Jing Chen,&nbsp;Qian Ding","doi":"10.1111/cns.70400","DOIUrl":"https://doi.org/10.1111/cns.70400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Inattention in young people is one of the main reasons for their declining learning ability. Frontoparietal networks (FPNs) are associated with attention and executive function. Brain computer interface (BCI) training has been applied in neurorehabilitation, but there is a lack of research on its application to cognition. This study aimed to investigate the effect of BCI on the attention network in healthy young adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-seven healthy people performed BCI training for 5 consecutive days. An attention network test (ANT) was performed at baseline and immediately after the fifth day of training and included simultaneous functional near-infrared spectroscopy recording.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BCI performance improved significantly after BCI training (<i>p</i> = 0.005). The efficiencies of the alerting and executive control networks were enhanced after BCI training (<i>p</i> = 0.032 and 0.003, respectively). The functional connectivity in the bilateral prefrontal cortices and the right posterior parietal cortex increased significantly after BCI training (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggested that repetitive BCI training could improve attention and induce lasting neuroplastic changes in FPNs. It might be a promising rehabilitative strategy for clinical populations with attention deficits. The right PPC may also be an effective target for neuromodulation in diseases with attention deficits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856971","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 Targets and Molecular Mechanisms of Calycosin in the Treatment of Depression: Insights From Chronic Mild Stress Animal Models","authors":"Guowei Gong,&nbsp;Yaqun Liu,&nbsp;Zhenxia Zhang,&nbsp;Yuzhong Zheng","doi":"10.1111/cns.70353","DOIUrl":"https://doi.org/10.1111/cns.70353","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Depression is a complex psychiatric disorder with limited therapeutic options and various side effects. Calycosin, a bioactive compound derived from <i>Astragalus membranaceus</i>, possesses multiple pharmacological properties. This study aimed to investigate the antidepressant effects of calycosin in chronic mild stress (CMS) animal models of depression and to elucidate its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The antidepressant effects of calycosin were assessed in vivo using CMS animal models of depression, including the grooming frequency test, sucrose intake test, tail suspension test, and open field test. Neurogenic effects were evaluated by measuring the levels of BDNF, GDNF, and NGF in isolated hippocampus tissues. The hepatoprotective effects were assessed by measuring liver enzyme levels. The molecular mechanisms underlying calycosin's antidepressant effects were explored in vitro using PC12 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Calycosin exhibited potent antidepressant-like activities in CMS animal models of depression. Treatment with calycosin significantly alleviated depressive symptoms and improved neurogenic effects. Additionally, calycosin displayed hepatoprotective effects by modulating liver enzymes in vitro. The antidepressant effects of calycosin are mediated by the stimulation of the TrkB–MEK–Erk1/2–CREB signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, calycosin shows promise as a novel therapeutic agent for depression due to its potent antidepressant-like activities and diverse pharmacological properties. Further studies are warranted to elucidate the exact molecular targets of calycosin and to assess its efficacy and safety in clinical settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856970","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":"Development of In Vitro Parkinson's Disease Model Mediated by MPP+ and α-Synuclein Using Wharton's Jelly Mesenchymal Stem Cells","authors":"Naisarg Gamit,&nbsp;Manasi Patil,&nbsp;B. S. Soumya,&nbsp;Arun Dharmarajan,&nbsp;Sudha Warrier","doi":"10.1111/cns.70299","DOIUrl":"https://doi.org/10.1111/cns.70299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Main Problem</h3>\u0000 \u0000 <p>The mechanism behind Parkinson's disease (PD) is still unclear, and a cure to stop its progression is yet to be found. This is mainly due to the lack of effective human PD models. To address this, we generated an in vitro PD model using Wharton's jelly-derived mesenchymal stem cells (WJMSCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>WJMSCs were isolated from the umbilical cord using an enzymatic method. MSCs were characterized by RT-PCR, immunofluorescence, and trilineage differentiation. MSCs were differentiated into dopaminergic neuron-like cells (DAN) and further degenerated by treating them with either MPP+ iodide or the A53T mutated α-synuclein variant. Gene expression analysis by qRT-PCR and protein analysis by immunofluorescence, flow cytometry, and ELISA were performed. Assays to measure LDH, ROS, NO, GSH, and mitochondrial membrane potential were also performed after degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WJMSCs were positive for MSC markers and were able to differentiate into adipocytes, chondrocytes, and osteocytes. DAN obtained after the differentiation of WJMSCs for 48 h expressed neuronal markers such as synapsin 1, neuropilin, neurofilament, and MAPT along with dopaminergic markers such as Nurr1, DAT, TH, DDC, and KCNJ6 and were functionally active. Upon degeneration of DAN by MPP+ or A53T, elevated levels of SNCA and downregulation of TH, Nurr1, DAT, and KCNJ6 were observed. Furthermore, increased expression of α-SYN was detected at the protein level as well. Finally, reduction in mitochondrial membrane potential and GSH levels along with an increase in intracellular ROS, nitrite production, and LDH levels confirmed that the in vitro PD-like model exhibited the molecular characteristics of PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This model is rapid, cost-efficient, and effective for understanding the molecular mechanisms of the disease and can also be used for screening of emerging therapeutics for PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856741","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 Between the Highest Lactate Level on the First Postoperative Day and Postoperative Delirium in Cardiac Surgery Patients","authors":"Ran An,&nbsp;Xie Wu,&nbsp;Dongyun Bie,&nbsp;Jie Ding,&nbsp;Yinan Li,&nbsp;Yuan Jia,&nbsp;Su Yuan,&nbsp;Fuxia Yan","doi":"10.1111/cns.70380","DOIUrl":"https://doi.org/10.1111/cns.70380","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The study aimed to determine the correlation between the maximum lactate on the first postoperative day and the incidence of postoperative delirium (POD) in patients after cardiac surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The data of cardiac surgery patients were extracted from the Medical Information Mart for Intensive Care IV database. The cut-off value for the first postoperative day maximum lactate was determined, and all patients were categorized into two groups according to the cut-off value. Propensity score matching (PSM) was applied between the two groups, and the difference in the incidence of POD was analyzed. Then, we employed univariate logistic regression, multivariate logistic regression, PSM, and inverse probability of treatment weighting (IPTW) models to examine the relationship between the first postoperative day lactate levels and POD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 4856 patients enrolled, there was a significant difference in lactate-max on the first postoperative day between patients without POD and patients with POD (median 2.5 vs. 3.1, <i>p</i> &lt; 0.001). The cut-off value of lactate-max was 2.85 mmol/L. For the two groups after PSM, the incidence of POD in the lactate-max ≥ 2.85 mmol/L group was significantly elevated (19.2% vs. 15.9%, <i>p</i> = 0.029). The elevated lactate-max on the first postoperative day was substantially associated with an increased risk of POD in univariate and multivariate logistic regression analyses, PSM, and IPTW models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results demonstrated that the first postoperative day lactate-max was correlated with the risk of POD in patients undergoing cardiac surgery, with the POD risk increasing significantly in patients with a lactate-max ≥ 2.85 mmol/L on the first postoperative day.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856972","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":"Gut Microbial Tryptophan Metabolism Is Involved in Post-Cardiac Arrest Brain Injury via Pyroptosis Modulation","authors":"Chenghao Wu,&nbsp;Mengyuan Diao,&nbsp;Shuhang Yu,&nbsp;Shaosong Xi,&nbsp;Zhipeng Zheng,&nbsp;Yang Cao,&nbsp;Shuai Wang,&nbsp;Ying Zhu,&nbsp;Mao Zhang,&nbsp;Wei Hu","doi":"10.1111/cns.70381","DOIUrl":"https://doi.org/10.1111/cns.70381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Post-cardiac arrest brain injury (PCABI) is a leading cause of death in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) victims and long-term disability in CA/CPR survivors. Despite previous evidence indicating that the microbiota-gut-brain axis is critically involved in many neurological disorders, no research has hitherto established a connection between the gut microbiota and PCABI through this axis. This study aims to explore the biological roles of microbial tryptophan metabolites in the progression of PCABI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To achieve this, we pretreated rats with a cocktail of broad-spectrum antibiotics (Abx) to eradicate the gut microbiota before establishing a 7-min asphyxia-CA/CPR model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Remarkably, the 24-h survival rate and neurological outcomes improved in Abx/CPR rats. Fecal 16s rDNA sequencing and PICRUSt2 analysis revealed that Abx reshaped the microbial community and elevated the proportion of microbial tryptophan metabolism in rats. Metabolomic profiling suggested that Abx shifted the phenotype of microbial tryptophan metabolism from the indole pathway to the kynurenine pathway, thereby increasing the levels of the neuroprotective metabolite kynurenine in the feces, circulation, and ultimately the brain. Furthermore, the hippocampal expression of aryl hydrocarbon receptor (AhR), an endogenous receptor of kynurenine, was upregulated in Abx/CPR rats. In vitro experiments further demonstrated that the neuroprotective effects of kynurenine are AhR-dependent and that AhR activation could negatively regulate the NLRP3 protein expression. Supporting this, results from qRT–PCR, immunohistochemistry, and immunofluorescence in the rat cerebral cortex exhibited that L-kynurenine inhibited NLRP3-induced pyroptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study provides a direct clue to the essential participation of the microbiota-gut-brain axis in the progression of PCABI. It demonstrates that kynurenine might attenuate PCABI by inhibiting NLRP3-induced pyroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856904","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":"Impact of Anesthesia on Brain Functional Networks in Moyamoya Disease and Spinal Lesions","authors":"Xuanling Chen,&nbsp;Xuewei Qin,&nbsp;Zhengqian Li,&nbsp;Shengpei Wang,&nbsp;Zhenhu Liang,&nbsp;Hua Zhang,&nbsp;Lan Yao,&nbsp;Xiaoli Li,&nbsp;Ran Duan,&nbsp;Rong Wang,&nbsp;Xiangyang Guo","doi":"10.1111/cns.70358","DOIUrl":"https://doi.org/10.1111/cns.70358","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To analyze the effects of intravenous propofol combined with remifentanil on whole-brain functional networks in patients with ischemic moyamoya disease (IMMD) and intraspinal space-occupying lesions (SOLs) using resting-state functional magnetic resonance imaging (rs-fMRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten patients with IMMD and 10 sex- and age-matched patients with lumbar SOL (normal cerebrovascular findings on preoperative MRI) were recruited. General anesthesia was administered using propofol and remifentanil. rs-fMRI imaging was performed in both awake and anesthetized states. Whole-brain functional network in different states was constructed based on graph theory tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In awake patients with IMMD, significant reductions in nodal strength (NS) were observed in the default mode network (DMN), sensorimotor network, and frontoparietal control network (FPN), compared to patients with SOL. Nodal efficiency (NE) showed further significant network declines. Under anesthesia, patients with IMMD: (1) exhibited disease-specific decreases in NS and NE across several networks, potentially reflecting underlying cerebral pathology. (2) Propofol's effects also contributed to significant NS and NE reductions in several brain regions. Changes before and after anesthesia in patients with IMMD were significantly decreased in specific regions (discussed in detail) per analysis of NS versus NE. DMN connectivity correlated moderately with Montreal Cognitive Assessment scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Reduced whole-brain functional connectivity in patients with IMMD before anesthesia was similar to the alterations caused by systemic intravenous drugs administered after anesthesia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ChiCTR2300075268</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852961","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":"WSO Action Plan for Stroke Prehospital Care: Top Two Priorities","authors":"Renyu Liu,&nbsp;Jing Zhao,&nbsp;Amit Kandel,&nbsp;Siju V. Abraham,&nbsp;Gary A Ford,&nbsp;Marc Fisher,&nbsp;Jeyaraj Durai Pandian","doi":"10.1111/cns.70374","DOIUrl":"https://doi.org/10.1111/cns.70374","url":null,"abstract":"<p>This editorial commentary describes the consensus reached by a group of experts from the World Stroke Organization regarding two top priorities to improve stroke prehospital care on the global stage. The first priority is effective stroke action awareness, and the second is the research and development of point-of-care prehospital diagnostic technologies.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852960","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":"Synergistic Inhibition of Nav1.7 and NCX1: A Novel Strategy for Treating Cancer-Induced Bone Pain by Modulating Pain Sensitization and Neuronal Inflammation","authors":"Yan Feng,&nbsp;Fang Yan,&nbsp;Dongtai Chen,&nbsp;Peizong Wang,&nbsp;Yan Yan,&nbsp;Xiangnan Chen,&nbsp;Qiang Li,&nbsp;Wei Xing,&nbsp;Weian Zeng,&nbsp;Yang Huang","doi":"10.1111/cns.70389","DOIUrl":"https://doi.org/10.1111/cns.70389","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cancer-induced bone pain (CIBP) is a chronic and refractory pain condition characterized by neuronal hyperexcitability, calcium dysregulation, and neuroinflammation. Voltage-gated sodium channels (VGSCs) and sodium/calcium exchangers (NCXs) are crucial in regulating sensory neuron sodium–calcium homeostasis, influencing nociceptive signaling and neuroinflammatory responses. This study focused on exploring how Nav1.7 from the VGSC family and NCX1 from the NCX family influence nociceptive signaling and neuroinflammation in CIBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CIBP was induced in mice. Nav1.7 and NCX1 expression and colocalization in DRG neurons were analyzed by qPCR, western blotting, and immunofluorescence. Calcium overload and neuronal excitability were assessed using calcium imaging and electrophysiological recordings. Neuroinflammation markers were detected by qPCR and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the VGSC and NCX subtypes, Nav1.7 and NCX1 were notably upregulated and colocalized in the DRG neurons of CIBP mice. Combined inhibition of these channels demonstrated a synergistic analgesic effect and markedly reduced neuronal calcium overload and hyperexcitability. Furthermore, the combined inhibition substantially alleviated neuroinflammation by inhibiting the p38 MAPK/NF-κB pathway and lowering proinflammatory cytokine levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The combined inhibition of Nav1.7 and NCX1 enhances analgesic effects and reduces neuroinflammation, presenting a potential therapeutic approach for CIBP and other cancer-associated pain disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846050","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}