CNS Neuroscience & Therapeutics最新文献

{"title":"Qishiwei Zhenzhu Pills Protect Against Cerebral Ischemia via the P53/Cytochrome C/Apoptotic Protease Activating Factor 1-Mediated Mitochondrial Apoptosis Pathway","authors":"Yinglian Song, Guili Song, Lame Lizhen, Yan Liang, Mengtian Han, Yichu Yang, Qiaoqiao Feng, Yi Li, Jingwen Zhang, Min Xu, Yongzhong Zeweng, Miao Jiang, Zhang Wang","doi":"10.1111/cns.70476","DOIUrl":"https://doi.org/10.1111/cns.70476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Qishiwei Zhenzhu pills (QSWZZP, Tibetan name: ) originated from Ershiwuwei Zhenzhu mother pills in the eighth century AD and are currently included in the <i>Chinese Pharmacopoeia</i> (2020). QSWZZP calm the mind, activate the medians, regulate qi, and harmonize the blood. QSWZZP have significant therapeutic effects in cerebral ischemia. However, QSWZZP's complex and diverse multi-herb chemical composition has presented challenges in identifying their active ingredients, which have hitherto remained unclarified. Therefore, the present study focusses on the identification of QSWZZP's active ingredients and their therapeutic mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To analyze the distribution of QSWZZP's components in the blood and tissues for the treatment of cerebral ischemia, to identify the biomarkers after drug intervention, and to explore the mechanism of action of QSWZZP in terms of the mitochondrial apoptosis pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used for qualitative and metabolomic analysis of the distribution of QSWZZP's components in the blood and tissues. A middle cerebral artery occlusion (MCAO) rat model was used to evaluate and measure neurobehavioral changes, the ratio of cerebral infarction, the rate of apoptosis-positive cells in the brain tissue, and the pathological changes in the cerebral cortex, hippocampus, and diencephalon. mRNA, protein, and fluorescence expressions of apoptosis-inducing factor (AIF), P53, cytochrome C (Cyt C), apoptotic protease activating factor-1 (APAF-1), cleaved caspase-8, B-cell lymphoma-extra-large, and N-myc downstream-regulated gene family member 4 (NDRG4) were determined in the rat brain tissues via real-time polymerase chain reaction, western blotting, and immunofluorescence. In addition, molecular docking was used to screen the active components of QSWZZP against mitochondria-mediated apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-three new compounds were identified, including 13 triterpenoids and nine flavonoids. Among them, 15 blood-entry, 21 urine-entry, three brain-entry, seven liver-entry, and four kidney-entry components were identified. QSWZZP significantly improved neurobehavioral abnormalities and reduced the cerebral infarction rate in the MCAO rats by significantly decreasing AIF, P53, Cyt C, APAF-1, and cleaved caspase-8 mRNA expressions and Cyt C and APAF-1 protein expressions, as well as increasing ND","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482165","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 Clinical Trials Landscape for Alzheimer's Disease","authors":"Guoping Shen,&nbsp;Xue Xu,&nbsp;Minping Li,&nbsp;Zaiyuan Sun,&nbsp;Linyu Wei,&nbsp;Zhezhi Deng,&nbsp;Zehuang Lin,&nbsp;Jianwen Huang,&nbsp;Weiwei Qi,&nbsp;Jia Xu","doi":"10.1111/cns.70492","DOIUrl":"https://doi.org/10.1111/cns.70492","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Not only drug and non-drug development but also non-therapeutic research in Alzheimer's disease (AD) clinical trials is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The participants were AD clinical trials obtained from the clinicaltrials.gov registry. The research objectives and interventions of those trials were analyzed. Bibliometric network analysis of those published articles in PubMed was also conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1681 clinical trials and 565 corresponding published articles in the past 20 years were included in the analysis. “Safety”, “dose”, “adverse events”, and “biomarker” were the most frequently used words that appeared in the title or abstract of published articles. The top three classes of 362 drugs were anti-Amyloid, enhancing acetylcholine, neurotransmitter, or targeting its receptor. The physical therapy, diet, and cognitive training ranked as the first three classes of non-drug therapy. Imaging, risk factors, and molecular biomarkers were the three most abundant categories in non-therapeutic research, and three fields of prevention, risk factors, and the dental or intestinal microbiome showed an escalated trend (All <i>P</i>_trend &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Dissusion</h3>\u0000 \u0000 <p>The results described a comprehensive landscape for the clinical studies of AD. Although most drugs treated AD abortively, the success of lecanemab and decanemab provides confidence for us to further study the pathogenesis of AD and explore new therapeutic targets to develop anti-AD drugs. Rising non-drug and non-therapeutic research will provide more possible methods for the treatment and prevention of AD in thefuture.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493003","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":"Abnormalities of Hippocampal Subfields in Individuals With Acute Carbon Monoxide Poisoning","authors":"Mengyue Tang,&nbsp;Ting Li,&nbsp;Yan Deng,&nbsp;Yifan Ji,&nbsp;Siyue Wang,&nbsp;Nian Liu,&nbsp;Xiaohua Huang,&nbsp;Xiaoming Zhang","doi":"10.1111/cns.70482","DOIUrl":"https://doi.org/10.1111/cns.70482","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To investigate alterations in hippocampal subfields in patients with acute carbon monoxide poisoning (ACMP) and explore their relationship with neurocognitive function.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Forty-seven ACMP patients and 29 age- and sex-matched healthy controls (HCs) were recruited. All ACMP patients underwent carboxyhemoglobin (COHb) assessment at admission and acquired MRI scans within 3 days post-exposure. Cognitive functions were assessed using the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA), and activities of daily living were evaluated using the Functional Independence Measure (FIM) and Barthel Index (BI). Differences in hippocampal volume between groups were analyzed using Analysis of Covariance (ANCOVA), and correlations with cognitive and functional scores were evaluated.&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;After follow-up, 27.66% (13/47) of ACMP patients developed Delayed Encephalopathy After Carbon Monoxide Poisoning (DEACMP). The COHb concentration was significantly higher in the DEACMP group (median 17.70% vs. 11.95%, &lt;i&gt;z&lt;/i&gt; = −2.225, &lt;i&gt;p&lt;/i&gt; = 0.026) compared to the Recovery group. The cognitive function scores, delayed memory-related sub-items scores derived from cognitive assessments, and activities of daily living scores in the DEACMP group were lower than those in the Recovery group (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). The ACMP group showed significant volume reduction in the bilateral whole hippocampus, cornu ammonis (CA) cornu ammonis 3, CA4, GC.ML.DG, Moleculat_layer, and right subiculum compared to HCs. The right subiculum and right CA4 volumes were smaller in the DEACMP group than in the Recovery group. The ROC curve analysis indicated that the combination of COHb concentration, MoCA, and FIM scores had good predictive value for DEACMP(the area under the ROC curve = 0.887, &lt;i&gt;p&lt;/i&gt; &lt; 0001). Correlation analysis showed that MoCA-delayed recall was positively associated with the volume of the left CA1 subfield (&lt;i&gt;r&lt;/i&gt; = 0.357, &lt;i&gt;p&lt;/i&gt; = 0.020), and MMSE-delayed recall was positively associated with the volume of the left presubiculum (&lt;i&gt;r&lt;/i&gt; = 0.323, &lt;i&gt;p&lt;/i&gt; = 0.037).&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;This study is the first to report specific hippocampal subfield alterations in ACMP patients, suggesting their potential as non-invasive markers of hippocampal injury. The hippocampal subfields may contribute to the development of DEACMP by modulating cognitive processes. These findings may impro","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339618","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":"Buyang Huanwu Decoction Modulates the Gut Microbiota–C/EBPβ/AEP Axis to Ameliorate Cognitive Impairment in Alzheimer's Disease Mice","authors":"Junyi Liang,&nbsp;Xiaohong Dong,&nbsp;Jianshe Yang,&nbsp;Niyuan Hu,&nbsp;Xiaoting Luo,&nbsp;Shuyuan Cong,&nbsp;Jing Chen,&nbsp;Weiming Zhao,&nbsp;Bin Liu","doi":"10.1111/cns.70480","DOIUrl":"https://doi.org/10.1111/cns.70480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral disturbances. Buyang Huanwu Decoction (BYHWD), a traditional Chinese herbal formulation, has demonstrated potential neuroprotective effects. This study aims to evaluate the therapeutic impact of BYHWD on cognitive impairments in 3×Tg mice and to investigate its underlying mechanism through modulation of the gut microbiota–C/EBPβ/AEP signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In two independent experiments, we assessed the effects of BYHWD and its derived fecal microbiota transplantation (FMT-BYHWD) on behavioral performance, neuropathological alterations, and signaling pathways in 3×Tg mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with BYHWD significantly improved cognitive function in 3×Tg mice and mitigated AD-like pathological changes. By suppressing the C/EBPβ/AEP signaling pathway, BYHWD reduced pathological Aβ plaque deposition, diminished tau hyperphosphorylation, and inhibited the release of pro-inflammatory cytokines. Further analysis revealed that BYHWD restored gut microbiota balance and suppressed the activation of the C/EBPβ/AEP pathway in the hippocampus. Moreover, transplanting FMT-BYHWD from BYHWD-treated mice to germ-free 3×Tg mice also ameliorated their cognitive deficits and AD-like pathology, suggesting that the anti-AD effects of BYHWD are mediated through the gut–brain axis by regulating the interplay between gut microbiota and the C/EBPβ/AEP signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers the mechanism by which BYHWD improves cognitive deficits and neuropathological changes in 3×Tg mice via the gut–brain axis, mediated by the modulation of the gut microbiota-C/EBPβ/AEP signaling pathway, providing a novel therapeutic strategy for AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339624","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 “Metrnl/C-KIT Axis Attenuates Early Brain Injury Following Subarachnoid Hemorrhage by Inhibiting Neuronal Ferroptosis”","authors":"","doi":"10.1111/cns.70494","DOIUrl":"https://doi.org/10.1111/cns.70494","url":null,"abstract":"<p>Zhou, Y., Li, J., Yuan, Y., Zhang, H., et al. (2025), Metrnl/C-KIT Axis Attenuates Early Brain Injury Following Subarachnoid Hemorrhage by Inhibiting Neuronal Ferroptosis. <i>CNS Neuroscience &amp; Therapeutics</i>, 31: e70286. https://doi.org/10.1111/cns.70286</p><p>In the original version of this article, there was an error in Figure 10L. Specifically, the TMRE representative image in Hb + r-Metrnl + ISCK03 group was incorrect. The correct image is provided below. The correction does not affect the results and conclusions.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339620","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":"Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte–Neuron Interaction in Cognitive Decline After High-Altitude Cerebral Edema","authors":"Wenying Lv,&nbsp;Yuehong Ma,&nbsp;Dongtao Li,&nbsp;Kexin Xiong,&nbsp;Jing Cui,&nbsp;Shuyi Pan,&nbsp;Ningkun Zhang,&nbsp;Yang Li,&nbsp;Yu Chen,&nbsp;Dazhi Guo","doi":"10.1111/cns.70485","DOIUrl":"https://doi.org/10.1111/cns.70485","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-altitude cerebral edema (HACE) leads to cognitive decline, but the underlying cellular and molecular mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a mouse model of HACE under hypobaric hypoxia (simulating at an altitude of 6000 m) and analyzed hippocampal changes using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) at 3 days and 7 days post-exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypobaric hypoxia induced HACE and cognitive decline by altering the transcriptomic profiles and interactions of oligodendrocytes (MOL and MOL2) and neurons (ExN-L6-CT-2). Early upregulation of PI3K/mTOR in oligodendrocytes mitigated Rps29-bax-mediated ribosomal stress and oxidative phosphorylation, promoting survival and myelin repair. Prolonged hypoxia suppressed PI3K/mTOR, triggering apoptosis/autophagy via oxidative phosphorylation and ribosomal stress. Enhanced Tnfrsf21-App interactions between MOL2 and ExN-L6-CT-2 exacerbated neuroinflammation and cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study reveals that HACE-induced cognitive impairment is closely associated with dysregulated ribosomal stress and oxidative phosphorylation and impaired neuroactive ligand-receptor interactions. Furthermore, we identify PI3K/mTOR dynamics, Rps29-bax-axis, and Tnfrsf21-App as novel regulators, offering potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339623","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":"Exploring the Influence of Left Dorsolateral Prefrontal Cortex Intermittent Theta-Burst Stimulation on Working Memory Load: An EEG Study in Healthy Participants","authors":"Ya-wen Li,&nbsp;Qian Ding,&nbsp;Jing Chen,&nbsp;Yu-hong Huang,&nbsp;Shan-tong Yao,&nbsp;Zheng-hong Chen,&nbsp;Yue Lan,&nbsp;Guang-qing Xu","doi":"10.1111/cns.70486","DOIUrl":"https://doi.org/10.1111/cns.70486","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Working memory (WM), a short-term cognitive process involving the prefrontal cortex, is critical for daily functioning. This study investigated the effects of iTBS on WM performance and its neural mechanisms in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-one healthy adults completed 1-back and 2-back tasks while undergoing EEG recording. Each received both active and sham iTBS over the left dorsolateral prefrontal cortex separately. Behavioral performance, EEG power, and functional connectivity were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Active iTBS significantly increased theta power in prefrontal cortices during the 1-back task. It also enhanced alpha band connectivity between the left prefrontal and right parietal cortices. In the 2-back task, iTBS increased beta band connectivity between the right prefrontal and right parietal cortices, and alpha band connectivity between the left and right parietal cortices. No significant behavioral differences were found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that iTBS effects on WM are primarily reflected in large-scale oscillatory network dynamics, rather than solely in localized cortical activity or behavioral performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70486","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323687","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 Administration of Circulating Extracellular Vesicles Modified by Anesthesia and Surgery Induces Delirium-Like Behaviors in Aged Mice","authors":"Yubo Gao,&nbsp;Shaling Tang,&nbsp;Jun Liu,&nbsp;Xiaoxia Yang,&nbsp;Hui Chen,&nbsp;Jiahui Li,&nbsp;Xinli Ni","doi":"10.1111/cns.70483","DOIUrl":"https://doi.org/10.1111/cns.70483","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The mechanisms by which peripheral surgery remotely affects brain function remain unclear. Circulating extracellular vesicles (EVs) are a complex membrane vesicle system composed of peripheral immune cells and other tissue sources. They can carry proteins and nucleic acids without being restricted by the blood–brain barrier. They transfer peripheral pro-inflammatory factors and damage proteins to the brain, regulate intracellular signaling by acting on specific cells, and therefore play a role in cell-to-cell communication. It remains uncertain whether postoperative delirium occurs after anesthesia and surgery because peripheral blood EVs transfer peripheral pathogenic factors into the brain, inducing pathological changes in neuronal cells and cognitive and behavioral abnormalities. This study aimed to investigate the effects of circulating EVs from mice under anesthesia and surgery on the cognitive behavior and neuronal cells of recipient mice through animal experiments. Moreover, the expression profiles of differential proteins and microRNAs were analyzed in circulating EVs from mice undergoing anesthesia and surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used aged mice and performed laparotomy under sevoflurane anesthesia to simulate the clinical environment. Twenty-four hours after anesthesia and surgery, circulating EVs were extracted and injected into the control mice via the tail vein to observe cognitive behaviors and neuronal pathological changes in the recipient mice. To further identify the key pathogenic factors in circulating EVs, we used high-throughput technology to detect the differential proteins and miRNAs in the circulating EVs of mice undergoing anesthesia and surgery compared to control mice. Candidate differential proteins and miRNAs were then screened and verified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The administration of anesthesia and surgery-derived EVs to control mice led to the manifestation of delirium-like behavioral changes and pathological changes in nerve cells in recipient mice. SAA1, miR-103-3p, and miR-31-5p are potential target molecules implicated in POD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Circulating EVs are novel potential mediators involved in POD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323437","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":"Network Topography Alterations in Alzheimer's Disease: Insights From Motif Changes via Multisite Datasets (N = 3262)","authors":"Juntao Zhao,&nbsp;Yunyun Duan,&nbsp;Kun Zhao,&nbsp;Hongwei Li,&nbsp;Dawei Wang,&nbsp;Hongxiang Yao,&nbsp;Bo Zhou,&nbsp;Jie Lu,&nbsp;Pan Wang,&nbsp;Yan Chen,&nbsp;Xi Zhang,&nbsp;Ying Han,&nbsp;Yong Liu,&nbsp;Zhengluan Liao","doi":"10.1111/cns.70428","DOIUrl":"https://doi.org/10.1111/cns.70428","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Convergent studies have demonstrated that the topological structure of the brain network undergoes significant alterations in Alzheimer's Disease (AD). However, the underlying mechanisms driving these topological changes remain unclear. Network motifs, as fundamental components of brain networks, provide valuable insights into how disconnections may lead to alterations in the macroscale topological structure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study focuses on undirected triangle motifs within the brain network, identifying 20 unique undirected triangle motifs based on edge strength and length derived from the regional radiomics similarity network (R2SN). To comprehensively capture the distribution of these motifs, we introduce a measure named Principal Motif Value (PMV) of the 20 motifs using principal component analysis (PCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings reveal significant spatial heterogeneity in PMV across different brain regions. In addition, we identify reproducible alterations of PMV in AD, which were observed through three independent datasets, particularly in the inferior temporal gyrus, middle temporal gyrus, and parahippocampal gyrus. Notably, PMV demonstrates significant correlations with clinical manifestations and neurological features. Finally, we elucidate that alterations in PMV are associated with gene expression related to neuronal systems and synapsis features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide novel insights into the relationship between disconnection and the topological structure of the brain network in AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323480","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 Relationship Between Glymphatic Function, White Matter Hyperintensity and Cognition: A Structural Equation Model MRI Study","authors":"Lin Wu,&nbsp;Kaixiao Chen,&nbsp;Zhi Zhang,&nbsp;Han Wang,&nbsp;Daojun Hong,&nbsp;Meng Li,&nbsp;Fuqing Zhou","doi":"10.1111/cns.70478","DOIUrl":"https://doi.org/10.1111/cns.70478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>White matter hyperintensity (WMH) is associated with glymphatic dysfunction. Few studies have focused on the causal effects of the dysfunction of the glymphatic circulation pathways (inflow and outflow pathway) on WMH and cognitive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study investigated the directional effects between glymphatic circulation, WMH lesions, and cognitive function in older adults based on structural equation models. The lateral ventricle choroid plexus (ChP), the coupling strength between blood oxygen signals in gray matter and cerebrospinal fluid flow, the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, and meningeal lymphatic vessels (MLVs) were analyzed for quantitative analysis of the glymphatic circulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to healthy controls, participants with WMH had greater ChP volume, lower DTI-ALPS index, and reduced MLVs function, all associated with worse cognitive performance. Both ChP/LatVent (<i>p</i> = 0.009) and DTI-ALPS (<i>p</i> &lt; 0.001) are significant predictors of WMH volume. Deep WMH (DWMH) partially mediated the relationship between glymphatic function (ChP/LatVent, <i>β</i> = 0.108, <i>p</i> = 0.044; DTI-ALPS, <i>β</i> = 0.122, <i>p</i> = 0.032) and cognition. Structural equation models revealed that glymphatic outflow negatively influenced WMH (<i>β</i> = −0.572, <i>p</i> &lt; 0.001), and WMH had a significantly negative effect on cognitive function (<i>β</i> = −0.705, <i>p</i> = 0.006).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that DWMH plays a mediating role in glymphatic decline and cognitive abnormalities, and that diminished glymphatic circulation affects WMH volume, leading to decreased cognitive function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323438","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}