CNS Neuroscience & Therapeutics最新文献

{"title":"Sirtuin1 in Spinal Cord Injury: Regulatory Mechanisms, Microenvironment Remodeling and Therapeutic Potential","authors":"Jinze Li,&nbsp;Shengyu Cui,&nbsp;Yanqiu Li,&nbsp;Can Zhang,&nbsp;Chao Chang,&nbsp;Fengzeng Jian","doi":"10.1111/cns.70244","DOIUrl":"https://doi.org/10.1111/cns.70244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) is a complex central nervous system disorder characterized by multifaceted pathological processes, including inflammation, oxidative stress, programmed cell death, autophagy, and mitochondrial dysfunction. Sirtuin 1 (Sirt1), a critical NAD⁺-dependent deacetylase, has emerged as a promising therapeutic target for SCI repair due to its potential to protect neurons, regulate glial and vascular cells, and optimize the injury microenvironment. However, the regulatory roles of Sirt1 in SCI are complex and challenging, as its effects vary depending on activation timing, expression levels, and cell types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature review was conducted using PubMed, Scopus, and Web of Science to identify studies investigating Sirt1 in SCI. Relevant publications were analyzed to synthesize current evidence on Sirt1's mechanisms, therapeutic effects, and challenges in SCI repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sirt1 exerts broad regulatory effects across diverse pathological processes and cell types post-SCI. It promotes neuronal survival and axonal regeneration, modulates astrocytes and microglia to resolve inflammation, supports oligodendrocyte-mediated myelination, and enhances vascular endothelial function. Proper Sirt1 activation may mitigate secondary injury, whereas excessive or prolonged activation could impair inflammatory resolution or disrupt cellular homeostasis. This review highlights Sirt1 activation as potential therapies, but challenges include optimizing spatiotemporal activation and addressing dual roles in different cell types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Targeting Sirt1 represents a viable strategy for SCI repair, given its multifaceted regulation of neuroprotection, immunomodulation, and tissue remodeling. However, translating these findings into therapies requires resolving critical issues such as cell type-specific delivery, precise activation timing, and dosage control. This review provides a theoretical foundation and practical insights for advancing Sirt1-based treatments for SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362344","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":"Identification of Depression Subtypes in Parkinson's Disease Patients via Structural MRI Whole-Brain Radiomics: An Unsupervised Machine Learning Study","authors":"Zihan Zhang,&nbsp;Jiaxuan Peng,&nbsp;Qiaowei Song,&nbsp;Yuyun Xu,&nbsp;Yuguo Wei,&nbsp;Zhenyu Shu","doi":"10.1111/cns.70182","DOIUrl":"https://doi.org/10.1111/cns.70182","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;Current clinical evaluation may tend to lack precision in detecting depression in Parkinson's disease (DPD). Radiomics features have gradually shown potential as auxiliary diagnostic tools in identifying and distinguishing different subtypes of Parkinson's disease (PD), and a radiomic approach that combines unsupervised machine learning has the potential to identify DPD.&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;Analyze the clinical and imaging data of 272 Parkinson's disease (PD) patients from the PPMI dataset, along with 45 PD patients from the NACC dataset. Extract radiomic features from T1-weighted MRI images and employ principal component analysis (PCA) for dimensionality reduction. Subsequently, apply four unsupervised clustering methods including Gaussian mixture model (GMM), hierarchical clustering, K-means, and partitioning around medoids (PAM) to classify cases in the PPMI dataset into distinct subtypes. Identify high-risk subtypes of DPD on the basis of the time and number of depression progression, and validate these findings using the NACC dataset. The data from the high-risk subtype were divided into a training subtype and a testing subtype in a 7:3 ratio. Multiple logistic regression analysis was conducted on the training subtype data to develop a traditional logistic regression model for the high-risk subtype, which was subsequently compared with a supervised logistic regression model constructed for the entire PPMI cohort. Finally, the performance of both models was evaluated using receiver operating characteristic (ROC) curves. In addition, a decision tree (DT) model was constructed based on independent risk factors of high-risk subtypes and validated using low-risk subtype data. ROC curves were employed to validate this model across training subtype, testing subtype, and low-risk subtype datasets.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The PAM clustering method demonstrates superior performance compared to the other three clustering methods when the number of clusters is 2. High-risk subtypes of DPD can be effectively distinguished in both the PPMI and NACC datasets. A traditional logistic regression model was developed based on rapid-eye-movement behavior disorder, UPDRS I score, UPDRS II score, and ptau in high-risk subgroups. This model exhibits a diagnostic efficacy (AUC = 0.731) that surpasses that of the traditional regression model constructed using the entire PPMI cohort (AUC = 0.674). The prediction model based on high-risk subtypes had AUC values of 0.853 and 0.81 in the training and testing subtypes, sensitivities of 0.765 and 0.786, and specificities of 0.771 and 0.815","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362811","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":"Hybrid PET/MRI Imaging of 18F-Fluorodeoxyglucose and 18-kDa Translocator Protein for Presurgical Localization in Refractory Epilepsy","authors":"Siqi Zhang,&nbsp;Jie Hu,&nbsp;Zhigang Qi,&nbsp;Chenyang Yao,&nbsp;Bixiao Cui,&nbsp;Jingjuan Wang,&nbsp;Zhenming Wang,&nbsp;Jie Lu","doi":"10.1111/cns.70251","DOIUrl":"https://doi.org/10.1111/cns.70251","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Surgery remains the only curative option for a third of refractory epilepsy patients, though success depends on precise localization of the epileptogenic zone (EZ). This study aims to assess the clinical value of hybrid ¹⁸F-FDG and ¹⁸F-DPA-714 PET/MRI for accurate localization and precise boundary delineation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The refractory epilepsy patients who underwent surgery at Xuanwu Hospital from November 2022 to November 2023 were retrospectively recruited. Preoperative simultaneous ¹⁸F-FDG and ¹⁸F-DPA-714 PET/MRI imaging were analyzed using the asymmetry index (AI) and a 4-point visual score, with the surgical site and pathological findings serving as the gold standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 43 patients (mean age: 26.30 ± 8.37 years, male: 28) were included in this study. Lesion localization accuracy within the EZ was 76.7% for ¹⁸F-FDG PET/MRI, 69.8% for ¹⁸F-DPA-714 PET/MRI, and 60.5% for conventional MRI (<i>p</i> = 0.26). In 26 MRI-positive cases, conventional MRI accurately localized all lesions within the EZ, with three cases showing negative findings on ¹⁸F-FDG images and six on ¹⁸F-DPA-714. Among 17 MRI-negative patients, thirteen demonstrated positive results on hybrid PET/MRI. Additionally, ¹⁸F-DPA-714 PET/MRI proved more effective in delineating lesion boundaries. Compared to ¹⁸F-FDG, the AI score was significantly lower (0.25 ± 0.18 vs. 0.46 ± 0.19, <i>p</i> &lt; 0.001), while the visual score was higher (4.00 ± 2.00 vs. 3.00 ± 0.00, <i>p</i> = 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>¹⁸F-DPA-714 PET/MRI can effectively complement conventional MRI in the preoperative assessment of refractory epilepsy, with localization accuracy on par with ¹⁸F-FDG and enhanced capability in delineating lesion boundaries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362808","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":"Berberine Alleviates Kainic Acid-Induced Acute Epileptic Seizures in Mice via Reshaping Gut Microbiota-Associated Lipid Metabolism","authors":"Wen-Ting Dai,&nbsp;Yong Zhu,&nbsp;Zui-Ming Jiang,&nbsp;Yi Xiang,&nbsp;Xiao-Yuan Mao,&nbsp;Zhao-Qian Liu","doi":"10.1111/cns.70253","DOIUrl":"https://doi.org/10.1111/cns.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Berberine (BBR) has been reported to mitigate epileptic seizures. However, the potential mechanism of its anti-seizure effect remains uncharacterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the protective effect of BBR on acute epileptic seizures induced by kainic acid (KA) in mice and further explore its mechanism of action in the aspect of analysis of gut microbiota.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The protective effect of BBR against acute epileptic seizures was assessed via Racine score and Nissl training. Alterations of gut microbiota and metabolites in seizure mice after BBR treatment were analyzed through 16S sequencing and lipidomics, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that the BBR remarkably alleviated acute epileptic seizures and hippocampal neuron damage in KA-induced mice. The analysis of gut microbiota indicated that BBR reduced the acute epileptic seizures in KA-induced mice by increasing the abundance of Bacteroidetes and Alloprevotella, regulating short-chain fatty acids (SCFAs). Results of lipidomics also identified 21 candidate metabolites in the colon and hippocampus possibly involved in the protective effect of BBR against acute seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that BBR exerts neuroprotection against KA-induced epileptic seizures through remodeling gut microbiota-associated lipid metabolism in the colon and hippocampus. BBR may serve as a valuable candidate drug for curing patients with epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362809","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":"Impaired Glymphatic Function in Acute Spontaneous Intracerebral Hemorrhage","authors":"Jinsong Cai,&nbsp;Yecheng Dong,&nbsp;Mengmeng Fang,&nbsp;Kai Wei,&nbsp;Shenqiang Yan,&nbsp;Ying Zhou","doi":"10.1111/cns.70252","DOIUrl":"https://doi.org/10.1111/cns.70252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Alterations in glymphatic function during the acute phase of acute spontaneous intracerebral hemorrhage (sICH) remain poorly understood. The aim of this study was to investigate whether, compared to healthy controls (HCs), the glymphatic system is impaired in patients with sICH, and to assess its association with hemorrhage and edema severity and outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-five sICH patients (including 46 supratentorial sICH and 9 <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mtext>subtentorial sICH</mtext>\u0000 </mrow>\u0000 <annotation>$$ mathrm{subtentorial} mathrm{sICH} $$</annotation>\u0000 </semantics></math>) and 97 age- and sex-matched HCs underwent conventional MRI and diffusion tensor imaging. The diffusion along the perivascular space (DTI-ALPS) index, serving as a marker for glymphatic function, was computed, with supratentorial cases being categorized into ipsilateral and contralateral ALPS. Volumes of hemorrhage and edema were evaluated using susceptibility-weighted imaging (SWI) and T2-weighted magnetic resonance images, and the relative edema ratio was calculated. Clinical outcomes were categorized as favorable or poor based on a modified Rankin scale score of ≤ 2 or &gt; 2 at 90 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>sICH patients showed significantly lower DTI-ALPS values on the ipsilateral side compared to the average in the HC group (1.34 ± 0.24 vs. 1.46 ± 0.22, <i>p</i> = 0.003), whereas contralateral DTI-ALPS values in sICH patients did not differ significantly from HCs (1.48 ± 0.21 vs. 1.46 ± 0.22, <i>p</i> = 0.524). The ipsilateral DTI-ALPS was notably associated with both hemorrhage and relative edema volumes (both <i>p</i> &lt; 0.05). A higher ipsilateral DTI-ALPS was independently associated with a favorable outcome at 90 days (odds ratio = 1.686 per 0.1 increase, <i>p</i> = 0.038).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The DTI-ALPS index, which reflects glymphatic functionality, is notably diminished on the ipsilateral side in acute sICH, correlating significantly with increased volumes of hemorrhage and edema. This study suggests that glymphatic dysfunction may contribute to the severity of clinical outcomes, and highlights the potential role of the glymphatic system in the pathophysiology of sICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248591","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":"miR-448-3p/miR-1264-3p Participates in Intermittent Hypoxic Response in Hippocampus by Regulating Fam76b/hnRNPA2B1","authors":"Chuncheng Liu,&nbsp;Donghui Qu,&nbsp;Chaoxun Li,&nbsp;Wenhua Pu,&nbsp;Jun Li,&nbsp;Lu Cai","doi":"10.1111/cns.70239","DOIUrl":"https://doi.org/10.1111/cns.70239","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intermittent hypoxia (IH), as a key pathogenic factor of obstructive sleep apnea syndrome (OSAS), can cause many diseases, such as increased inflammation and oxidative stress, diabetes, cardiovascular disease, and Alzheimer's disease (AD). The response of cells to hypoxia involves multiple levels of regulatory mechanisms, including transcriptional regulation of gene expression, regulation of mRNA stability, post-transcriptional regulation, and post-translational modification regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The regulation of miRNA and alternative splicing (AS) in neuronal response to intermittent hypoxia deserve further study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>By establishing a mouse model of intermittent hypoxia, we conducted functional studies on key miRNAs and splicing factor using methods such as miRNA sequencing, bioinformatics, and molecular biology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the mouse hippocampus, intermittent hypoxia altered the expression of many miRNAs, with miR-448-3p and miR-1264-3p changing over the course of more than three time periods. Interestingly, the expression of <i>Fam76b</i>, the common target gene of these two miRNAs, also changed under intermittent hypoxia. Further studies showed that Fam76b may regulate the ratio of <i>Nbr1</i> and <i>Dph3</i> transcripts in response to hypoxia by affecting the localization of hnRNPA2B1 protein within cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Research into intermittent hypoxia-induced disorders, including Alzheimer's disease and other neurodegenerative diseases, might benefit from a better understanding of the regulatory mechanisms of miRNA and alternative splicing in hypoxic response at the animal and cell levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that intermittent hypoxia alters the expression of miR-448-3p and miR-1264-3p, as well as the localization of the splicing factor hnRNPA2B1 in the cell nucleus. These findings enhance our understanding of the molecular mechanisms of neuronal responses to hypoxia and hold potential implications for treating hypoxia-related diseases like Alzheimer's disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248592","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":"LncRNA-MEG3 Mediated Diabetic Cerebral Ischemia–Reperfusion Injury-Induced Apoptosis via Modulating Interaction Between Annexin A2 and Akt in Mitochondria","authors":"Wanqing Zhou,&nbsp;Chongyi Tan,&nbsp;Di Xiong,&nbsp;Cheng Chen,&nbsp;Yanfei Zhao,&nbsp;Yongqiu Xie,&nbsp;Bei Sun,&nbsp;Zhihua Wang,&nbsp;Pingping Xia,&nbsp;Zhi Ye","doi":"10.1111/cns.70242","DOIUrl":"https://doi.org/10.1111/cns.70242","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;In clinical domains, encompassing neurosurgery and macrovascular cardiac procedures, certain interventions result in cerebral ischemia- reperfusion injury (CIRI). Diabetes mellitus (DM) increases the risk of CIRI and worsens the severity of neurological impairment. It was documented that lncRNA-MEG3 contributed to the pathogenesis of CIRI. However, the pivotal significance of lncRNA-MEG3 in diabetic CIRI has never been studied.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study's aims were two-fold, to (1) figure out the influence of lncRNA-MEG3 on neurological dysfunction subsequent to diabetic cerebral ischemic injury, (2) elucidate its potential role in mitochondria-related apoptosis via modulating the Anxa2 signaling pathway.&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;We mainly collected plasma from clinical patients to measure the expression of lncRNA-MEG3, and explored the molecular mechanism of lncRNA-MEG3 in CIRI combined with DM by immunofluorescence, western blot, co-ip and other molecular biology experiments in rat MACO+DM model and cellular OGD/R+HG model.&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;LncRNA-MEG3 expression in DM+AIS cases was remarkably higher than that in cases with AIS and healthy controls. Moreover, lncRNA-MEG3 expression was strongly linked to the National Institutes of Health Stroke Scale (NIHSS) score. Additionally, the findings unveiled that lncRNA-MEG3 depletion alleviated neurological impairments following CIRI in diabetic rats, and cellular death resulted from Oxygen-glucose deprivation (OGD) plus hyperglycemic reperfusion in rat brain microvascular endothelial cells (RBMVECs) that was concomitant with the increased phosphorylation of Annexin A2 (Anxa2) at Tyr23. Meanwhile, over expression of Anxa2, identified as a lncRNA-MEG3-associated mitochondrial protein, remarkably suppressed mitochondria-derived apoptosis. Importantly, lncRNA-MEG3 knockdown enhanced the mitochondrial translocation of Anxa2 via promoting its phosphorylation at Tyr23 in OGD+HG-treated RBMVECs. Furthermore, Anxa2 enhanced Akt phosphorylation at Ser473 and bound to Akt in mitochondria, which was involved in lncRNA-MEG3 depletion-induced neuroprotection. However, lncRNA-MEG3 mobilized to mitochondria in a Plectin-dependent manner and subsequently impeded the interaction between p-Anxa2 and p-Akt.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion and Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The outcomes provided ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248876","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":"Regulatory T Cells for Stroke Recovery: A Promising Immune Therapeutic Strategy","authors":"Ning Li,&nbsp;Hujun Wang,&nbsp;Changbin Hu,&nbsp;Shuyan Qie,&nbsp;Zongjian Liu","doi":"10.1111/cns.70248","DOIUrl":"10.1111/cns.70248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions and neuroprotection during the acute phase, there has been a growing focus on tissue repair and functional recovery in the subacute and chronic phases after stroke. The pro-inflammatory microglial polarization occurs in subacute and chronic phases after stroke and may represent therapeutic targets for stroke recovery. CD4⁺ regulatory T cells (Tregs), a subtype of T cells with immunosuppressive effects, have been shown to be important in stroke. Tregs infiltrate into the brain primarily during the subacute and chronic phases following a stroke. Infiltrating Tregs play a critical role in mitigating pro-inflammatory microglial responses, modulating the immune microenvironment, and promoting the functional restoration of the damaged brain following a stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was conducted in PubMed, Scopus, and Web of Science and then conduct a comprehensive analysis of the searched literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review provides a comprehensive summary of recent preclinical research advances on the role of Tregs in stroke, with a particular focus on their reparative functions during the subacute and chronic phases. It discusses changes in peripheral and brain infiltrating Tregs post-stroke, their functions and underlying mechanisms, and therapeutic strategies involving Tregs. Additionally, this review explores the potential and challenges associated with the clinical application of Tregs in ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treg cell-related therapy represents a promising immune-therapeutic strategy for stroke recovery. However, there are several critical issues that must be resolved before its advancement to clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057433","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":"Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease","authors":"Huan Yi,&nbsp;Jie Zhang,&nbsp;Kai Gao,&nbsp;Wei Yan,&nbsp;Hongyuan Chu,&nbsp;Junjiao Zhang,&nbsp;Fan Zhang,&nbsp;Yuwu Jiang,&nbsp;Jingmin Wang,&nbsp;Ye Wu","doi":"10.1111/cns.70240","DOIUrl":"10.1111/cns.70240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Alexander disease (AxD) is a leukodystrophy caused by mutations in the astrocytic filament gene <i>GFAP</i>. There are currently no effective treatments for AxD. Previous studies have rarely established AxD models with the patient's original GFAP mutations. In this study, we aimed to explore the morphological and transcriptomic characteristics of GFAP-mutant astrocytes via induced pluripotent stem cell (iPSC) models of AxD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fibroblasts from three AxD children were reprogrammed into iPSCs. Wild-type (WT) and AxD-iPSCs were differentiated into astrocytes. We compared the morphological and transcriptomic differences between WT- and AxD iPSC–derived astrocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Astrocytes induced from AxD-derived iPSCs exhibited the Rosenthal fibers (RFs), the main pathological phenotype of AxD. Compared with WT astrocytes, AxD astrocytes had shorter processes, more branches, and larger cell bodies. Transcriptomic analysis revealed that extracellular matrix (ECM) components, particularly chondroitin sulfate proteoglycans (CSPGs), were upregulated, and ECM-degrading enzymes were generally downregulated. These changes may lead to abnormalities in neurons and myelination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We explored the morphological characteristics of AxD astrocytes via iPSC models and revealed the ECM, previously unexplored for AxD, may be an important new pathogenic mechanism of this disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045112","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":"Disrupted Cross-Scale Network Associated With Cognitive-Emotional Disorders in Sudden Sensorineural Hearing Loss","authors":"Biao Li,&nbsp;Xiao-Min Xu,&nbsp;Yuan-Qing Wu,&nbsp;Yuan Feng,&nbsp;Yu-Chen Chen,&nbsp;Richard Salvi,&nbsp;Jin-Jing Xu,&nbsp;Jian-Wei Qi","doi":"10.1111/cns.70234","DOIUrl":"10.1111/cns.70234","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;Sudden sensorineural hearing loss (SSNHL) is associated with abnormal changes in the brain's central nervous system. Previous studies on the brain networks of SSNHL have primarily focused on functional connectivity within the brain. However, in addition to functional connectivity, structural connectivity also plays a crucial role in brain networks. Moreover, traditional functional connectivity analyses often overlook the spatial and temporal characteristics of connectivity changes and fail to provide directional information and causal relationships.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study utilized Structural Covariance Network (SCN), multilayer network analysis, and Dynamic Causal Modeling (DCM) to investigate the cross-scale changes in neural network structure and function in SSNHL patients with accompanying cognitive and emotional disorders.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials &amp; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We collected 3D-T1 structural magnetic resonance image data and functional magnetic resonance image data from 70 SSNHL patients and 81 healthy controls (HCs). SCN analysis was performed based on gray matter volume, and multilayer network analysis was used to calculate node switching rates. Based on the results of multilayer network analysis, six nodes exhibiting significant inter-group differences in node switching rates were selected as regions of interest (ROIs). DCM was then conducted to explore the causal relationships of functional connectivity between these nodes.&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;Based on SCN, there were no significant inter-group differences in global network properties between SSNHL and HCs. At the node level, the left precentral gyrus in SSNHL showed a significant decrease in node efficiency. In the multilayer network analysis, SSNHL showed a significantly increased node switching rate at the level of the Left Superior Frontal Gyrus (L.SFG), Left Supplementary Motor Area (L.SMA), Left Superior Parietal Gyrus (L.SPG), Right Superior Parietal Gyrus (R.SPG), Right Inferior Parietal Lobe(R.IPL), and Left Thalamus (L.THA). Furthermore, the node switching rate of L.SFG showed a significant negative correlation with the Self-Rating Anxiety Scale (SAS) scores. DCM analysis of these six nodes revealed differences in the functional effective connectivity between the left superior parietal gyrus (L.SPG) and the left supplementary motor area (L.SMA), which were positively correlated with the AVLT-delay scores.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;sec","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045109","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}