CNS Neuroscience & Therapeutics最新文献

{"title":"Decoding Post-Stroke Cognitive Impairment After Acute Basal Ganglia Infarction: The Synergistic Role of Functional Segregation and Integration in an SVM fMRI Framework","authors":"Shijian Chen,&nbsp;Jian Zhang,&nbsp;Liya Pan,&nbsp;Baohui Weng,&nbsp;Yijie Mo,&nbsp;Xuemei Quan,&nbsp;Gengyu Cen,&nbsp;Xize Jia,&nbsp;Yayuan Liu,&nbsp;Zhijian Liang","doi":"10.1002/cns.70871","DOIUrl":"10.1002/cns.70871","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether dynamic changes in resting-state functional MRI (rs-fMRI) metrics can serve as sensitive biomarkers for distinguishing acute basal ganglia cerebral infarction (BGCI) patients with post-stroke cognitive impairment (PSCI) from those without (non-PSCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Data on various rs-fMRI metrics dynamic functional connectivity (dFC), dynamic amplitude of low-frequency fluctuation (dALFF), and percent amplitude of fluctuation (PerAF) were acquired using a Siemens Prisma 3.0T scanner from 38 PSCI and 36 non-PSCI patients, with follow-up assessments. Functional segregation and integration were analyzed using PerAF, dALFF, and dFC. Feature extraction and selection were performed using support vector machine (SVM), followed by classifier construction and evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with PSCI showed decreased PerAF in the left cerebellar Crus I (lCbeCru1) and increased dALFF in the right cerebellar Crus I and left lingual gyrus compared to non-PSCI patients. Altered dFC was observed between cerebellar cognitive-related seed regions and widespread cortical areas, with increased dFC in the right cerebellar Crus II and left cuneus, and decreased dFC primarily in the inferior frontal gyrus and superior temporal gyrus. Among single-feature models, dFC achieved the best classification performance (AUC = 0.98, accuracy = 94.52%, sensitivity = 97.14%, specificity = 92.11%, precision = 91.89%). A combined feature model yielded the highest precision (94.12%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SVM-based integration of PerAF, dALFF, and dFC features holds promise as a neuroimaging biomarker for PSCI in patients with BGCI. This approach may support more precise early rehabilitation strategies in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653529","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":"Astrocyte-Derived Exosomal miR-211-5p Alleviates Blood–Brain Barrier Injury in a Rat Model of Traumatic Brain Injury","authors":"Yan Chen,&nbsp;Xuan Yin,&nbsp;Erwei Zhang,&nbsp;Bin Li,&nbsp;Huijie Yu,&nbsp;Jiawang Qi,&nbsp;Minghao Liu,&nbsp;Meng Wang,&nbsp;Zhenzeng Fan,&nbsp;Lijun Yang","doi":"10.1002/cns.70858","DOIUrl":"10.1002/cns.70858","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) triggers a cascade of secondary damage, including neuroinflammation, astrocyte activation, and disruption of the blood–brain barrier (BBB), all of which contribute to long-term neurological deficits. Astrocyte-derived exosomes have emerged as a promising therapeutic avenue; however, the specific contributions of their molecular cargo remain poorly understood. This study explores whether astrocyte-derived exosomal delivery of microRNA-211-5p (miR-211-5p) can attenuate secondary injury and enhance functional recovery following TBI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary astrocytes were transfected with AAV-rno-miR-211-5p, and the resulting exosomes were isolated and characterized. TBI was induced in adult rats using a controlled cortical impact (CCI) model. Exosomes (1 × 10¹¹ particles) were administered intravenously 30 min post-injury. Behavioral assessments were conducted to evaluate cognitive function and neurological deficits. Brain edema, glial activation, and the expression of inflammatory cytokines (IL-6, IL-1β, TNF-α) and BBB-related markers—including glial fibrillary acidic protein (GFAP), matrix metalloproteinase 9 (MMP9), aquaporin 4 (AQP4), and the tight junction proteins zonula occludens-1 (ZO-1) and claudin-5—were analyzed using quantitative real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and histopathological techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Exosomes enriched with miR-211-5p significantly improved cognitive and neurological outcomes, reduced cerebral edema, and downregulated the expression of GFAP, MMP9, and AQP4. Furthermore, the integrity of the BBB was preserved, as evidenced by sustained expression of ZO-1 and claudin-5. Levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α were also markedly decreased in the injured cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Astrocyte-derived exosomal miR-211-5p confers neuroprotection in TBI by modulating glial activation, reducing neuroinflammation, and preserving BBB integrity. These findings underscore the therapeutic potential of miR-211-5p-loaded exosomes as a cell-free, targeted intervention for brain trauma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637417","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":"Forsythoside A Alleviates Neuroinflammatory Damage via Inhibiting TLR4/NF-κB/NLRP3 Activation-Induced Astrocyte Pyroptosis in Cerebral Ischemia–Reperfusion","authors":"Yupeng Guo,&nbsp;Xuanwei Dong,&nbsp;Min Liu,&nbsp;Jianxin Wang,&nbsp;Shewei Guo","doi":"10.1002/cns.70867","DOIUrl":"10.1002/cns.70867","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The neuroinflammatory cascade triggered by cerebral ischemia–reperfusion injury (CIRI) represents a pivotal pathological mechanism driving neuronal death and dysfunction. Forsythoside A (FA) exhibits anti-inflammatory properties, but its effects on CIRI and potential mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate whether FA improves astrocyte pyroptosis and alleviates neuroinflammatory damage in CIRI via modulating the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The middle cerebral artery occlusion reperfusion (MCAO/R) mouse model was established, with cerebral infarction volume observed through TTC staining, and neurological scores assessed. The effects of FA on cerebral cortical damage, neuroinflammation, apoptosis, and pyroptosis were observed by pathological staining. An oxygen–glucose deprivation/reoxygenation (OGD/R) U251 human astroglioma cell model was established, and the protective impact of FA on cell viability was detected through the cell counting kit-8 assay. The release of lactate dehydrogenase (LDH) was measured by the LDH assay Kit, and cell pyroptosis was evaluated through Hoechst 33,342/PI staining. Inflammatory factor levels were detected by ELISA kits, with pyroptosis-related and TLR4/NF-κB/NLRP3 pathway-related protein levels evaluated through Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FA reduced the infarct volume, ameliorated brain tissue pathological damage, reduced activated astrocytes, and inhibited neuronal apoptosis in MCAO/R mice. FA also alleviated inflammatory cell infiltration in brain tissue and declined pro-inflammatory factor levels in serum. In addition, FA suppressed TLR4 and p-NF-κB p65 expression and NLRP3 inflammasome activation in astrocytes. OGD/R caused decreased U251 cell viability, increased LDH release, and pyroptosis rate, while FA treatment could reverse the above effects. Mechanistically, FA hindered the TLR4/NF-κB pathway, down-regulated NLRP3 and pyroptosis-related proteins. The TLR4 agonist LPS weakened the protective impact of FA on MCAO/R mice and OGD/R cell models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FA alleviates neuroinflammatory damage through inhibiting the TLR4/NF-κB axis and blocking NLRP3 inflammasome-induced astrocyte pyroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632167","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":"Olink Proteomics Reveals CCL2 Aggravates Perihematomal Edema After Intracerebral Hemorrhage in High-Altitude Migrants Via CCR2/NF-κB-Mediated Blood–Brain Barrier Disruption","authors":"Rongsu Huang,&nbsp;Ling Gao,&nbsp;Yalan Dai,&nbsp;Shangshi Li,&nbsp;Jiancai Guru,&nbsp;Mingxi Li,&nbsp;Yù-Jié Chen,&nbsp;Bo Wu,&nbsp;Xufang Ru,&nbsp;Qing Gong,&nbsp;Jun Tang,&nbsp;Gang Zhu,&nbsp;Yujie Chen","doi":"10.1002/cns.70868","DOIUrl":"10.1002/cns.70868","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To identify key environment-sensitive inflammatory factors and clarify their pathogenic mechanisms in severe secondary brain injury after intracerebral hemorrhage (ICH) in high-altitude migrants—addressing the critical gap that elevated hemoglobin alone cannot fully explain the underlying pathogenesis and investigating chronic inflammation as a key pathogenic driver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Olink proteomics profiling was performed in 66 high-altitude migrants and 22 plain-resident controls to identify differentially expressed inflammatory factors. Rat high-altitude ICH models were subsequently established and treated with AAV-CCL2, a CCL2-neutralizing antibody, recombinant CCL2, and a CCR2 inhibitor, and the results were validated through transcriptomic and multidimensional methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CCL2 was the most significantly upregulated environmentally sensitive inflammatory factor and was weakly correlated with hemoglobin levels. High-altitude rats had higher levels of post-ICH CCL2, which was associated with severe blood–brain barrier (BBB) disruption; CCR2 blockade abolished CCL2-induced BBB damage and neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CCL2 plays an important role in secondary injury after high-altitude ICH, mainly by amplifying inflammation and exacerbating damage via the CCL2–CCR2–NF-κB pathway and may serve as a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626576","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":"Electroacupuncture Modulates Multiple Pathways for Neuroprotection and Neurorepair in Ischemic Stroke","authors":"Mingyue Zhao,&nbsp;Hangyu Shen,&nbsp;Xu Yan,&nbsp;Xiang Gao,&nbsp;Yuchun Liu,&nbsp;Shengjun Zhou,&nbsp;Jingxian Sun,&nbsp;Jie Sun,&nbsp;Yi Huang","doi":"10.1002/cns.70862","DOIUrl":"10.1002/cns.70862","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The complex pathophysiology of ischemic stroke (IS) involves initial injury followed by secondary cascades and endogenous repair. This review systematically explores how electroacupuncture (EA) precisely modulates these processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched and summarized all papers related to EA treatment for stroke using the China National Knowledge Infrastructure (CNKI) and PubMed databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We detail EA's key mechanisms in reducing initial and secondary damage, including the suppression of inflammatory responses (e.g., NF-κB, inflammasomes, gut-brain axis), mitigation of oxidative stress (Nrf2/HO-1), attenuation of excitotoxicity (NMDAR, GLT-1), and inhibition of diverse forms of regulated cell death (apoptosis, pyroptosis, ferroptosis). Critically, EA also actively promotes vital repair mechanisms by enhancing cerebral blood flow, protecting blood–brain barrier integrity, promoting angiogenesis (VEGF, HIF, Notch, Wnt pathways), and fostering extensive neural regeneration and plasticity (neurogenesis, neurotrophic factors, myelination, synaptic changes, network reorganization) at molecular, cellular, and network levels. These well-documented mechanistic actions provide a strong scientific basis for the observed clinical benefits of EA in improving major poststroke sequelae, encompassing motor, cognitive, language, and emotional deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The review highlights the potential for enhanced outcomes through combined therapy approaches and identifies future research avenues leveraging advanced technologies like multi-omics and AI for personalized precision EA. EA stands as a scientifically grounded, multi-target therapy improving stroke recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626542","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 Viloxazine Paradox: A Noradrenergic Agent's Journey From Antidepressant Obscurity to ADHD Precision Therapy","authors":"Ghaith K. Mansour,&nbsp;Sabry Babiker H. Sayed,&nbsp;Sajjad Ghanim Al-Badri,&nbsp;Mohammed Gamaleldin Abdulrahim Abdalla,&nbsp;Dina Essam Abo-elnour","doi":"10.1002/cns.70839","DOIUrl":"10.1002/cns.70839","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Viloxazine is a serotonin–norepinephrine modulatory agent that was recently approved by the U.S. Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. This review aims to summarize the regulatory history, pharmacology, pharmacokinetics, clinical efficacy, safety, and current therapeutic role of viloxazine, while also highlighting gaps in the evidence and future research directions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A narrative literature review was conducted using PubMed, Google Scholar, and FDA regulatory documents. Relevant peer-reviewed articles, including clinical trials, reviews, meta-analyses, and prescribing information, were screened for data on viloxazine's historical antidepressant use, mechanism of action, pharmacokinetics, efficacy in ADHD, safety profile, drug interactions, and comparative effectiveness. Non-peer-reviewed sources were excluded.&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;Viloxazine was originally marketed in Europe in the 1970s as an antidepressant and showed a favorable safety profile over decades of use. Its pharmacological profile includes moderate norepinephrine reuptake inhibition with additional serotonergic activity, particularly 5-HT2C agonism and 5-HT2B antagonism, which supported its repurposing as an extended-release formulation for ADHD. Multiple randomized, placebo-controlled trials demonstrated that viloxazine extended-release significantly improves ADHD symptoms in pediatric, adolescent, and adult populations. Reported effect sizes were generally smaller than those of stimulants but comparable to atomoxetine. The most common adverse events were somnolence, headache, nausea, decreased appetite, and insomnia. Viloxazine also has a pharmacokinetic profile compatible with once-daily dosing, although clinically relevant drug interactions may occur through CYP1A2 inhibition.&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;Viloxazine expands the range of non-stimulant treatment options for ADHD and represents a successful example of drug repurposing in neuropsychiatry. Current evidence supports its efficacy and acceptable tolerability across the lifespan, particularly for patients who do not tolerate or respond adequately to stimulants. Nevertheless, evidence for its use beyond ADHD remains limited, and future studies should focus on head-to-head comparisons with other ADHD therapies, long-term safety and efficacy, predictors of response, and potential off-label psychiatric applicat","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632133","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":"Shared and Specific Patterns of Brain Functional Network Abnormalities in Patients With Idiopathic Dystonia and Across Subtypes","authors":"Gang Liu,&nbsp;Jiana Zhang,&nbsp;Yiheng Gao,&nbsp;Shiyuan Gong,&nbsp;Yuhan Luo,&nbsp;Linchang Zhong,&nbsp;Zilin Ou,&nbsp;Zhicong Yan,&nbsp;Weixi Zhang,&nbsp;Kangqiang Peng,&nbsp;Huiming Liu,&nbsp;Qingmao Hu,&nbsp;Jinping Xu","doi":"10.1002/cns.70816","DOIUrl":"10.1002/cns.70816","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Accumulating neuroimaging evidence showed that idiopathic dystonia is a large-scale network disorder, but whether the various clinical sub-types shared imaging abnormalities remains controversial. We aimed to determine whether various forms of idiopathic dystonia have common topological changes or are distinct entities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Resting-state functional magnetic resonance imaging and clinical data were obtained from 215 patients with various forms of dystonia and 160 healthy controls (HCs). Whole-brain functional networks were constructed, and the topological parameters were calculated via graph theoretical analyses. Networks were compared between patients with idiopathic dystonia and HCs and in subgroup analyses (each dystonia subtype vs. HCs; one-to-one and one-to-many comparisons among blepharospasm [BSP], blepharospasm-oromandibular dystonia [BOD], and cervical dystonia [CD] subgroups). Then, we analyzed the relationship between network topological changes and clinical characteristics in patients with idiopathic dystonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to HCs, patients with idiopathic dystonia exhibited alterations in network integration and segregation. Subgroup analyses revealed similar changes in BSP and BOD but not in CD. Regionally, degree centrality and nodal efficiency (Ne) in the somatomotor network of patients with idiopathic dystonia decreased and increased in the subcortical and cerebellar networks. Decreased nodal clustering coefficient (Ncp) and nodal local efficiency were observed in the visual and subcortical networks. Similar regional alterations were observed in patients with BSP. Patients with idiopathic dystonia showed additional hub regions. Correlation analyses showed that higher Ne in visual and cerebellar networks correlated positively, and lower Ncp correlated negatively in the visual network with motor severity in patients with BSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that patients with BSP and BOD share extensive reorganization in the large-scale functional network.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632106","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":"Efficacy and Safety of Zonisamide Addition in Children With Developmental Epileptic Encephalopathy/Epileptic Encephalopathy: A Real-World Study","authors":"Peijiao Liu,&nbsp;Li Zhang,&nbsp;Qiao Zeng,&nbsp;XiaoYu Zhao,&nbsp;Li Jiang,&nbsp;Yue Hu","doi":"10.1002/cns.70865","DOIUrl":"10.1002/cns.70865","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the real-world effectiveness and safety of adjunctive zonisamide in children with developmental epileptic encephalopathy/epileptic encephalopathy (DEE/EE), focusing on younger children and highly drug-resistant cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This open-label, nonrandomized, self-controlled, real-world study included 127 children with DEE/EE at a single center from 2020 to 2025. The primary endpoint was the responder rate (≥ 50% seizure reduction) at 3, 6, 9, and 12 months, analyzed using last observation carried forward. Secondary endpoints included seizure freedom, retention, and adverse events (AEs). Multivariable analysis identified predictors of efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Responder rates were 51.2%, 55.3%, 53.7%, and 53.7% at 3, 6, 9, and 12 months, respectively. Seizure-free rates were 23.6%, 26.8%, 24.4%, and 27.6%. Efficacy was consistent across age and etiology. Female gender (OR = 3.00) and fewer prior anti-seizure medications (OR = 0.77) independently predicted 12-month response. Among children failing ≥ 5 prior medications, 44.3% responded, and 20.0% achieved seizure freedom. The 12-month retention rate was 81.9%. AEs occurred in 14.2%, most commonly reduced appetite (7.9%); most were tolerable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adjunctive zonisamide provides sustained efficacy and favorable tolerability in children with DEE/EE, including young children &lt; 6 years and highly drug-resistant cases. Gender and prior treatment history predict long-term efficacy, supporting its reliable risk–benefit profile for refractory epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615529","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 Dual Role of Gastrodin in Spinal Cord Injury: Microglial Phenotype Switching and Neuronal Survival via PI3K/AKT Activation","authors":"Jingsheng Feng,&nbsp;Shutao Gao,&nbsp;Yukun Hu,&nbsp;Weibin Sheng","doi":"10.1002/cns.70811","DOIUrl":"10.1002/cns.70811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) triggers a complex secondary cascade, the defining feature of which is neuroinflammation. This amplifies tissue damage and impedes neurological recovery. Microglial polarization is a critical event in this process, yet effective modulation strategies remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate whether gastrodin (GAS), a natural phenolic glycoside, could provide neuroprotection and promote functional recovery following SCI by modulating microglial polarization and to elucidate the underlying molecular mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a combination of behavioral, histological, and molecular assays, and a microglia–neuron co-culture system under inflammatory conditions, using a rat contusion SCI model and LPS-stimulated BV2 microglia in vitro. The role of the PI3K/AKT signaling pathway was specifically investigated using the inhibitor LY294002.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The administration of GAS markedly enhanced locomotor function, diminished lesion volume, and promoted neuronal survival in a dose-dependent manner in vivo. GAS mitigated the inflammatory response by reducing M1 markers (iNOS and CD86) and augmenting M2 markers (Arg1 and CD206) within the injured spinal cord and BV2 microglia. Additionally, GAS exhibited a direct anti-apoptotic effect on neurons in co-culture. Mechanistically, GAS significantly activated the PI3K/AKT signaling pathway. Notably, the PI3K inhibitor LY294002 completely nullified the anti-inflammatory and anti-apoptotic effects of GAS, underscoring the central role of this pathway in mediating GAS's effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that GAS confers multifaceted protection against SCI by modulating microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and by directly inhibiting neuronal apoptosis, primarily through activation of the PI3K/AKT signaling pathway. These findings indicate that GAS holds significant potential as a therapeutic candidate for the treatment of SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615453","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":"Perivascular SPP1 Drives Microglial Synaptic Engulfment After Ischemic Stroke.","authors":"Chenchen Xu, Xiaoxiao Li, Nan Cheng, Rui Zhao, Xin Wang, Wenxin Xia, Jianjian Dong, Yongsheng Han","doi":"10.1002/cns.70886","DOIUrl":"https://doi.org/10.1002/cns.70886","url":null,"abstract":"<p><strong>Objective: </strong>Following ischemic stroke (IS), activated microglia activity could contribute to neuronal injury and blood-brain barrier (BBB) disruption. The upstream vascular-derived signal initiating this transition remains unclear; therefore, we investigated whether perivascular SPP1 regulates microglia-mediated synapse engulfment during IS.</p><p><strong>Methods: </strong>Male C57BL/6 mice were assigned to sham, shSpp1, middle cerebral artery occlusion/reperfusion (MCAO/R), and MCAO/R + shSpp1 groups. Cerebral perfusion was assessed using laser speckle contrast imaging and super-resolution vascular imaging, while neuronal injury was evaluated using Nissl and TUNEL staining. Proteomic profiling of the ischemic penumbra identified regulators of microglia-mediated synaptic remodeling. Synaptic structure and glial-vascular unit (GVU) integrity were examined using transmission electron microscopy, immunofluorescence, and molecular analyses. Behavioral outcomes were assessed using the open-field, Barnes maze, rotarod, and wire-hanging tests.</p><p><strong>Results: </strong>Compared with sham controls, MCAO/R mice displayed increased microglial synaptic engulfment and ultrastructural synaptic damage in the ischemic penumbra, accompanied by reduced synaptic protein expression. Proteomic analysis revealed upregulation of inflammatory and vascular-related pathways, with marked upregulation of SPP derived from perivascular macrophages. Spp1 silencing attenuated neuroinflammation, reduced infarct volume, improved cerebral perfusion, preserved GVU integrity, and alleviated behavioral deficits. Spp1 suppression also reduced microglial synaptic engulfment in vivo and restored synaptic protein and mRNA levels in vitro.</p><p><strong>Conclusion: </strong>Targeting perivascular SPP1 suppresses excessive microglia-mediated synaptic engulfment, preserves BBB integrity and synaptic architecture, and offers a GVU-centered therapeutic strategy for IS.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70886"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758241","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}