CNS Neuroscience & Therapeutics最新文献

{"title":"Proteomic Analyses of Clots Identify Stroke Etiologies in Patients Undergoing Endovascular Therapy","authors":"Tae Jung Kim,&nbsp;Jin Woo Jung,&nbsp;Young-Ju Kim,&nbsp;Byung-Woo Yoon,&nbsp;Dohyun Han,&nbsp;Sang-Bae Ko","doi":"10.1111/cns.70340","DOIUrl":"https://doi.org/10.1111/cns.70340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the correlation between clot composition and stroke mechanisms in patients undergoing endovascular therapy (EVT), using proteomic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 35 patients with ischemic stroke (cardioembolism [CE], <i>n</i> = 17; large artery atherosclerosis [LAA], <i>n</i> = 6; cancer-related [CR], <i>n</i> = 4; and undetermined (UD) cause, <i>n</i> = 8) who underwent EVT. Retrieved clots were proteomically analyzed to identify differentially expressed proteins associated with the three stroke mechanisms and to develop the machine learning model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the discover stage, 3838 proteins were identified using clot samples from 27 patients with CE, LAA, and CR mechanisms. Through functional enrichment and network analysis, 149 proteins were identified as potential candidates for verification studies. After verification experiments, 34 proteins were selected as the final candidates to predict stroke mechanisms. Furthermore, the machine learning-based model identified three proteins associated with each mechanism (Pleckstrin in CE; CD59 glycoprotein in LAA; and Immunoglobulin Heavy Constant Gamma 1 in CR) in the UD group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified specific protein markers of clots that could differentiate stroke mechanisms in patients undergoing EVT. Therefore, our results could offer valuable insights into elucidating the mechanisms of ischemic stroke, which could provide information on more effective secondary prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612469","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":"Anwulignan Alleviates Bone Cancer Pain by Modulating the PPARα/CXCR2 Signaling Pathway in the Rat Spinal Cord","authors":"Yueliang Wang,&nbsp;Qingying Liu,&nbsp;Yingying Jiang,&nbsp;Longfei Mao,&nbsp;Mohamed Zoubaa,&nbsp;Jian Wang,&nbsp;Huilian Bu,&nbsp;Minyu Ma,&nbsp;Jingjing Yuan,&nbsp;Jing Cao,&nbsp;Xiaochong Fan","doi":"10.1111/cns.70302","DOIUrl":"https://doi.org/10.1111/cns.70302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Advanced cancer patients frequently endure severe pain from bone metastases, and few effective treatments for bone cancer pain (BCP) exist. Although Anwulignan is known for its antioxidant, anti-inflammatory, and antitumor properties, its effects on BCP remain unclear. This study aims to explore the analgesic effects and mechanisms of Anwulignan on bone cancer pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Western blotting and immunofluorescence assessed molecular expression and localization. X-ray, micro-CT, TRAP, and ALP staining examined bone destruction in rats. MTT, colony formation assays, and in vivo imaging analyzed tumor changes. RNA-Seq identified differentially expressed genes, validated by ChIP analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we showed that Anwulignan alleviated mechanical, thermal, and cold hypersensitivity and spontaneous pain, prevented bone destruction, and suppressed local tumor growth in rats with BCP. Furthermore, Anwulignan was firmly bound to proliferator-activated receptor alpha (PPARα), increasing its thermal stability. Intrathecal (i.t.) injection of PPARα siRNA increased pain sensitivity in naive rats, and PPARα siRNA abrogated the analgesic effect of Anwulignan in BCP model rats. Moreover, the PPARα agonist pirinixic acid reduced BCP hypersensitivity and abrogated the upregulation of CXC chemokine receptor 2 (CXCR2). Importantly, PPARα bound to the CXCR2 promoter region, and Anwulignan could reverse the reduced binding of PPARα to CXCR2 caused by BCP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these results indicate that Anwulignan is a potential antitumor and analgesic agent that exerts its effects via upregulation of PPARα expression to inhibit the expression of CXCR2 and could be used for treating BCP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612414","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":"Applications and Predictors of Outcomes Following Stereo-Electroencephalography in Pediatric Patients With Drug-Resistant Epilepsy","authors":"Qingzhu Liu,&nbsp;Chang Liu,&nbsp;Shuang Wang,&nbsp;Taoyun Ji,&nbsp;Yu Sun,&nbsp;Guojing Yu,&nbsp;Yao Wang,&nbsp;Hao Yu,&nbsp;Yuwu Jiang,&nbsp;Xiaoyan Liu,&nbsp;Lixin Cai","doi":"10.1111/cns.70332","DOIUrl":"https://doi.org/10.1111/cns.70332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to evaluate the role of stereo-electroencephalography (SEEG) in managing pediatric patients with drug-resistant epilepsy. We further explore prognostic factors influencing surgical outcomes following SEEG-guided resective or disconnective surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review was conducted on pediatric patients who underwent SEEG at the Pediatric Epilepsy Center, Peking University First Hospital, between July 2017 and July 2022. Univariate and multivariate analyses identified key predictors for SEEG-guided surgery. Kaplan–Meier survival analysis was employed to estimate the seizure-free rate, and further statistical tests were applied to evaluate factors associated with seizure outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 148 children included in this study, 102 underwent SEEG-guided resective/disconnective surgery. Multivariate regression identified age at surgery (<i>p</i> &lt; 0.05, 95% CI 0.190–0.997) as an independent predictor for selecting resective/disconnective surgery. The seizure-free rate in patients who underwent SEEG-guided surgery was 69.6%. Multivariate regression confirmed that total resection with lesional MRI (<i>p</i> &lt; 0.05, 95% CI 0.012–0.186) and FCD type II (<i>p</i> &lt; 0.05, 95% CI 0.051–0.851) were strong predictors of seizure freedom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SEEG plays a crucial role in pediatric epilepsy surgery, particularly in children under 6 years old. Total resection with lesional MRI and FCD type II was the most favorable prognostic predictor for achieving seizure freedom in children undergoing SEEG-guided surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602506","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 Early Blood Pressure Levels and Outcomes in Ischemic Stroke Treated With Intravenous Thrombolysis: A Prospective Cohort Study","authors":"Luyi Zhu,&nbsp;Jiali Xie,&nbsp;Qingjian Xie,&nbsp;Yiting Xu,&nbsp;Yinuo Chen,&nbsp;Yaojia Li,&nbsp;Junwei Zhang,&nbsp;Chunyang Pang,&nbsp;Lingfei Gao,&nbsp;Huan Yu,&nbsp;Binbin Deng","doi":"10.1111/cns.70318","DOIUrl":"https://doi.org/10.1111/cns.70318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Current guidelines for acute ischemic stroke (AIS) treatment recommend a lenient upper blood pressure (BP) threshold of 185/110 mmHg. However, stricter BP control has been reported to improve prognosis. This study aims to identify the optimal BP range following thrombolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational study included 340 AIS patients treated with rt-PA thrombolysis at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to December 2021. BP levels 24 h after thrombolysis were analyzed to determine their association with clinical outcomes. BP parameters included mean BP, variability (standard deviation (SD)), and decreased magnitudes. The primary outcome was the 90-day modified Rankin Scale (mRS) scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher mean systolic BP (SBP) was associated with poorer outcomes, with adjusted odds ratios (aORs) of 1.25 (95% CI, 1.03–1.51), 1.23 (1.01–1.49), and 1.25 (1.02–1.52) per 10 mmHg increase within 0–2 h, 2–6 h, and 6–24 h post-thrombolysis, respectively, but not for BP variability and decrease magnitudes. Significant improvements in outcomes were observed when the mean SBP was maintained within the range of 120–140 mmHg during both the 0–2 and 2–6 h periods, with aORs of 0.12 (95% CI, 0.02–0.75) and 0.19 (0.04–0.82), respectively. Larger decreases in SBP within 6 h post-thrombolysis were associated with a lower risk of intracerebral hemorrhage. These findings were consistent across subgroups and sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Achieving sustained low SBP levels (120–140 mmHg within the first 6 h) over 24 h is linked to better outcomes in thrombolyzed AIS patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612497","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":"Correction to “RNF122 Promotes Glioblastoma Growth via the JAK2/STAT3/c-Myc Signaling Axis”","authors":"","doi":"10.1111/cns.70317","DOIUrl":"https://doi.org/10.1111/cns.70317","url":null,"abstract":"<p>Xiao Q, Xue K, Li L, Zhu K, Fu R, Xiong Z, RNF122 Promotes Glioblastoma Growth via the JAK2/STAT3/c-Myc Signaling Axis, CNS Neuroscience &amp; Therapeutics 30, (2024): e70017 10.1111/cns.70017.</p><p>In the original version of our article, there was an error in Figure 6A. Specifically, the representative image of A-172 (oeRNF122 + WP1066) cells in Figure 6A is incorrect. The correct image is provided below. This correction will not affect the results and conclusions.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612499","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":"A Novel Nomogram Integrating Retinal Microvasculature and Clinical Indicators for Individualized Prediction of Early Neurological Deterioration in Single Subcortical Infarction","authors":"Chen Ye,&nbsp;William Robert Kwapong,&nbsp;Le Cao,&nbsp;Hui Xu,&nbsp;Yanan Wang,&nbsp;Yuying Yan,&nbsp;Ruosu Pan,&nbsp;Ruilin Wang,&nbsp;Kun Lu,&nbsp;Lanhua Liao,&nbsp;Tang Yang,&nbsp;Shuai Jiang,&nbsp;Xuening Zhang,&nbsp;Wendan Tao,&nbsp;Junfeng Liu,&nbsp;Bo Wu","doi":"10.1111/cns.70337","DOIUrl":"https://doi.org/10.1111/cns.70337","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Early neurological deterioration (END) is a relatively common occurrence among patients with single subcortical infarctions (SSI). Accurate and early prediction of END in SSI is challenging and could contribute to enhancing prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective observational study enrolled SSI patients who arrived within 24 h from symptom onset at a single center between December 2020 and March 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the predictive model. A nomogram was generated based on multivariate logistic regression analysis to identify potential predictors associated with the risk of END. The performance and clinical utility of the nomogram were generated using Harrell's concordance index, calibration curve, and decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 166 acute SSI patients, 45 patients (27.1%) developed END after admission. The appearance of END is associated with four routine clinical factors (NIHSS score, serum neuron-specific enolase, uric acid, periventricular white matter hyperintensity), and two retinal microvascular indicators (ipsilateral superficial and deep vascular complexes). Incorporating these factors, the nomogram model achieved a concordance index of 0.922 (95% CI 0.879–0.964) and had a well-fitted calibration curve and good clinical application value by DCA. A cutoff value of 203 was determined to predict END via this nomogram.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This novel nomogram exhibits high accuracy in predicting END in SSI patients. It could guide clinicians to identify SSI patients with a high risk of END at an early stage and initiate necessary medical interventions, ultimately leading to a better prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612577","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":"Sequential Proteomic Analysis Reveals the Key APOE4-Induced Pathological and Molecular Features at the Presymptomatic Stage in Alzheimer's Disease Mice","authors":"Pengju Wei,&nbsp;Kaihua Lin,&nbsp;Xuhui Chen,&nbsp;Cheng Fang,&nbsp;Linhui Qiu,&nbsp;Jun Hu,&nbsp;Junlei Chang","doi":"10.1111/cns.70306","DOIUrl":"https://doi.org/10.1111/cns.70306","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) involves a prolonged presymptomatic or preclinical stage with subtle pathological changes. Apolipoprotein E4 (APOE4) is a significant genetic risk factor for AD, yet its specific role at the presymptomatic stage is not fully understood. This study aimed to elucidate the cellular and molecular effects of APOE4 compared to APOE3 on AD progression during the presymptomatic stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated <i>5xFAD</i> AD mice carrying human APOE3 or APOE4 and their non-AD controls. Behavioral tests, immunostaining, quantitative proteomics and phosphoproteomics, Golgi staining, and Western blotting were conducted at 3 or 10 months of age, respectively. Cell culture experiments were performed to assess APOE4's direct impact on neuronal mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>APOE4 significantly increased β-amyloid (Aβ) deposition and microglial activation compared to APOE3 in <i>5xFAD</i> mice at the presymptomatic stage, without aggravating the blood–brain barrier disruption. Proteomic and biochemical analysis revealed strong molecular features of synaptic degeneration and mitochondrial dysfunction associated with APOE4. Notably, APOE4 promoted mitochondrial fusion and mitophagy while inhibiting fission, leading to impaired neuronal energy supply and increased reactive oxygen species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that APOE4 accelerates AD pathologies at the presymptomatic stage by exacerbating Aβ deposition, neuroinflammation, and synaptic degeneration. The study highlights mitochondrial dysfunction as a critical mediator of APOE4-induced AD progression, providing potential targets for early intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612498","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":"Comments on “H4K12 Lactylation-Activated Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury”","authors":"Jieqi Zhang,&nbsp;Kelin He,&nbsp;Ruijie Ma","doi":"10.1111/cns.70339","DOIUrl":"https://doi.org/10.1111/cns.70339","url":null,"abstract":"<p>We read with great interest the recent study by Wang et al. [<span>1</span>] on the role of H4K12 lactylation (H4K12la) in promoting Spp1 transcription and facilitating functional recovery after spinal cord injury (SCI). The work provides novel insights into the relationship between metabolic reprogramming in microglia and neurorepair. By utilizing recombinant Spp1 protein (rSPP1), the authors have demonstrated its significant role in functional recovery, and we believe this study has important implications for spinal cord injury research.</p><p>We would like to offer a few suggestions that could further strengthen the study's reliability and completeness.</p><p>First, regarding the overexpression experiments, the authors used recombinant Spp1 protein (rSPP1) to investigate its effects on functional recovery following SCI. It is crucial to confirm the successful overexpression of Spp1 protein. Given that the half-life of recombinant proteins may vary depending on their properties and the administration route, confirming the protein expression levels at different time points will be essential for understanding its biological effects [<span>2, 3</span>]. We recommend the inclusion of Western blot (WB) results for both the vector group and recombinant Spp1 protein group at multiple time points to verify the expression levels of Spp1, particularly to confirm the duration of stable overexpression. This will help assess whether the overexpression effect of Spp1 is maintained during critical time windows of the experiment, which will strengthen the reliability of the observed functional recovery results.</p><p>Additionally, while the authors conducted separate experiments with neurons and microglia, there was no mention of coculture experiments involving both cell types. We suggest the authors include coculture experiments to investigate the bidirectional interaction between Spp1 in neurons and microglia, particularly how Spp1 may promote neuronal recovery by modulating the activation of microglia. This would offer a more comprehensive understanding of the mechanism by which Spp1 contributes to SCI repair.</p><p>Overall, we commend the authors for their innovative work and believe that their findings significantly advance our understanding of Spp1 in spinal cord injury repair. We look forward to further exploration of Spp1 and its regulatory mechanisms in this context.</p><p>Thank you for considering our suggestions, and we anticipate the continued development and refinement of this important work.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612578","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":"The Restoration of Energy Pathways Indicates the Efficacy of Ketamine Treatment in Depression: A Metabolomic Analysis","authors":"Zerui You,&nbsp;Xiaofeng Lan,&nbsp;Chengyu Wang,&nbsp;Haiying Liu,&nbsp;Weicheng Li,&nbsp;Siming Mai,&nbsp;Haiyan Liu,&nbsp;Fan Zhang,&nbsp;Guanxi Liu,&nbsp;Xiaoyu Chen,&nbsp;Yanxiang Ye,&nbsp;Yanling Zhou,&nbsp;Yuping Ning","doi":"10.1111/cns.70324","DOIUrl":"https://doi.org/10.1111/cns.70324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Despite the clinical benefits of ketamine in treating major depressive disorder (MDD), some patients exhibit drug resistance, and the intricate mechanisms underlying this await comprehensive explication. We used metabolomics to find biomarkers for ketamine efficacy and uncover its mechanisms of action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 40 MDD patients treated with ketamine in the discovery cohort and 24 patients in the validation cohort. Serum samples from the discovery cohort receiving ketamine were analyzed using ultra performance liquid chromatography-mass spectrometry to study metabolomic changes and identify potential biomarkers. Metabolic alterations were evaluated pre- and post-ketamine treatment. Spearman correlation was applied to examine the relationship between metabolite alterations and depressive symptom changes. In addition, potential biomarkers, particularly thyroxine, were investigated through quantitative measurements in the validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that energy metabolite changes (adenosine triphosphate, adenosine diphosphate [ADP], pyruvate) were different in responders versus non-responders. The magnitude of the ADP shift was strongly correlated with the rate of reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores (Rho = 0.48, <i>p</i>_FDR = 0.018). Additionally, baseline free triiodothyronine (FT3) levels are inversely associated with the rate of MADRS reduction (Rho = −0.645, <i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Ketamine ameliorates depressive symptoms by modulating metabolic pathways linked to energy metabolism. Low baseline FT3 levels appear to predict a positive response in MDD patients, suggesting FT3 has potential as a biological marker for clinical ketamine treatment.</p>\u0000 \u0000 <p><b>Trial Registration:</b> ChiCTR-OOC-17012239</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581636","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":"Neural Correlates and Adaptive Mechanisms in Vascular Cognitive Impairment: Exploration of a Structure–Function Coupling Network","authors":"Jing Jin,&nbsp;Jie Ma,&nbsp;Jia-Jia Wu,&nbsp;Juan-Juan Lu,&nbsp;Hao-Yu Lu,&nbsp;Mou-Xiong Zheng,&nbsp;Xu-Yun Hua,&nbsp;Jian-Guang Xu","doi":"10.1111/cns.70205","DOIUrl":"https://doi.org/10.1111/cns.70205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral small vessel disease exacerbates cognitive decline, yet the structural–functional coupling mechanisms in vascular cognitive impairment (VCI) remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 121 participants, with 68 individuals with VCI and 53 healthy controls. Participants underwent neuropsychological assessments and multimodal imaging. We compared white matter integrity, structural network topology, and functional network topology between groups, exploring the relationship between structure–function coupling and cognitive function. Family-wise error (FWE) correction was applied to account for multiple comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VCI participants showed reduced fractional anisotropy and increased mean and radial diffusivity in white matter. Structural network analysis revealed lower global and local efficiency, reduced small-world properties, and increased characteristic path length. Nodal properties, particularly in key regions of the default mode and visual networks, were significantly altered in VCI participants. While no significant differences were observed in functional network topology, VCI participants exhibited enhanced structure–function coupling in critical nodes of the default mode and visual networks. This enhancement correlated with memory function and information processing speed in the temporal calcarine, insula, occipital, and lingual regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study identifies disrupted brain networks and enhanced compensatory mechanisms in VCI, offering insights into neuroplasticity in VCI and contributing to dementia prevention strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581639","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}