CNS Neuroscience & Therapeutics最新文献

{"title":"Metabolic Signatures and Diagnostic Strategies for Different Types of Encephalitis","authors":"Yue Cui,&nbsp;Haitian Nan,&nbsp;Zhen Wang,&nbsp;Daiquan Gao,&nbsp;Hong Ye,&nbsp;Yunzhou Zhang,&nbsp;Junjie Li,&nbsp;Weibi Chen,&nbsp;Lin Wang,&nbsp;Jing Zhang,&nbsp;Liyong Wu","doi":"10.1002/cns.71014","DOIUrl":"10.1002/cns.71014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To characterize metabolic signatures associated with different encephalitis types and to develop differential diagnostic models based on metabolic dysregulation profiling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Untargeted metabolomics was performed on cerebrospinal fluid (CSF) from a prospective cohort of 232 patients classified into viral encephalitis (VE, <i>n</i> = 82), autoimmune encephalitis (AE, <i>n</i> = 63), other infectious encephalitis (OIE, <i>n</i> = 25), and non-encephalitis control (NE, <i>n</i> = 62) groups, with follow-up samples from 10 participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with controls, taurine-associated metabolites were consistently downregulated across the encephalitis groups. Arginine and proline metabolism were identified as commonly dysregulated pathways in the encephalitis groups. Highly similar metabolic network topologies were observed between VE and AE, despite different key node metabolites (lysophosphatidylcholine vs. acylcarnitine, respectively). Three diagnostic models developed to distinguish VE from other groups achieved an area under the receiver operating characteristic curve &gt; 0.8 in the training and validation sets. Glial fibrillary acidic protein antibody-positive AE exhibited a unique carnitine metabolism signature. Longitudinal follow-up identified seven metabolites significantly associated with clinical remission in patients with AE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study systematically maps shared and distinct metabolic perturbations in different types of encephalitis and suggests potential metabolic features associated with AE subtype-specific pathophysiology, providing a preliminary metabolomic basis for precision diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417121","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":"Oral Lysozyme Attenuates Neuroinflammation and Brain Injury After Traumatic Brain Injury Through Gut Microbiota-Dependent Reprogramming of Tryptophan Metabolism","authors":"Zhuoying Du,&nbsp;Haijun Yao,&nbsp;Caihua Xi,&nbsp;Qiang Yuan,&nbsp;Pengfei Fu,&nbsp;Jin Hu,&nbsp;Gang Wu,&nbsp;Weijian Yang","doi":"10.1002/cns.71025","DOIUrl":"10.1002/cns.71025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) induces secondary neuroinflammation and gut dysbiosis. This study investigated whether oral lysozyme confers neuroprotection after TBI through gut microbiota-dependent metabolic reprogramming of tryptophan metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a severe TBI mouse model, neurological function, neuroinflammation, intestinal barrier integrity, and systemic immune homeostasis were assessed following oral lysozyme administration. Fecal untargeted metabolomics, antibiotic-mediated microbiota depletion, and fecal microbiota transplantation (FMT) were used to explore microbiota involvement. Cerebrospinal fluid (CSF) from 10 matched pairs of patients with severe TBI was analyzed for tryptophan pathway metabolites by liquid chromatography–mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lysozyme improved neurological outcomes, attenuated neuronal apoptosis and neuroinflammation, and restored peripheral CD4⁺/CD8⁺ T cell homeostasis. Metabolomics revealed enrichment of fecal tryptophan metabolites (indole-3-carboxaldehyde, indolelactic acid, kynurenic acid [KYNA]) and a shift in cerebral kynurenine metabolism toward the KYNA branch. These associations were abolished by microbiota depletion and reproduced by FMT. Favorable clinical outcomes were associated with higher CSF KYNA and an elevated KYNA/QA ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Oral lysozyme was associated with attenuated TBI-induced neuroinflammation and brain injury, potentially through gut microbiota-dependent tryptophan metabolism reprogramming. Concordance between preclinical and clinical metabolomic data supports lysozyme as a candidate microbiota-targeted therapeutic strategy. The KYNA/QA ratio warrants further validation as a prognostic indicator in larger, longitudinal cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417185","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":"Plasma Metabolomics of Thrombectomy-Treated Patients Highlights Metabolic Pathways Underlying Disease and Recovery","authors":"Min Cai,&nbsp;Xiangyu Hou,&nbsp;Shilong Deng,&nbsp;Wenxin Shen,&nbsp;Dingzhi Gao,&nbsp;Xinyu Zhang,&nbsp;Siyuan Fan,&nbsp;Yongliang Xia,&nbsp;Yuanlin Ma,&nbsp;Ke Cheng","doi":"10.1002/cns.71018","DOIUrl":"10.1002/cns.71018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Thrombosis, characterized by pathological intravascular clot formation, underlies major clinical events such as cerebral infarction, myocardial infarction, and pulmonary embolism. However, metabolomic alterations associated with cerebral infarction, particularly those distinguishing patients with different clinical outcomes after recanalization, remain poorly characterized. This study aimed to provide an unbiased, systems-level characterization of metabolic alterations in cerebral infarction thrombosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed LC–MS/MS-based untargeted plasma metabolomics in both positive and negative ion modes. The cohort included 24 patients with meaningful functional recovery after cerebral infarction thrombectomy (MFR), 21 patients with futile recanalization (FTR), and 20 healthy controls (CON). Global metabolomic profiles were analyzed using multivariate and univariate approaches, followed by KEGG pathway enrichment analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasma metabolite profiles differed significantly among groups. Both MFR and FTR patients exhibited marked metabolic perturbations relative to controls, while the MFR group showed subtle but distinct metabolic patterns compared with FTR patients. Differential metabolites were enriched in pathways related to mitochondrial function, lipid signaling, amino acid metabolism, and inflammatory regulation, which are associated with endothelial function and thrombo-inflammatory responses in cerebral infarction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies metabolic alterations associated with cerebral infarction thrombosis and clinical outcome status following recanalization. These findings highlight candidate metabolites and pathways that may inform future mechanistic studies and biomarker validation specific to cerebral infarction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409836","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":"Colchicine as an Adjunctive Therapy to Improve Ischemic Stroke Reperfusion Outcomes in Mice","authors":"Danni Wang,&nbsp;Yuwen Xiu,&nbsp;Mengxuan Shi,&nbsp;Yingjie Wang,&nbsp;Di Zhou,&nbsp;Mitchell D. Kilgore,&nbsp;Lauren Dumont,&nbsp;Thin Yadanar Sein,&nbsp;Yinghua Jiang,&nbsp;Nicole Kazour,&nbsp;Ning Liu,&nbsp;Aaron S. Dumont,&nbsp;Qiang Liu,&nbsp;Xiaoying Wang","doi":"10.1002/cns.70922","DOIUrl":"10.1002/cns.70922","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;Mechanical thrombectomy (MT) has become a cornerstone therapy for acute ischemic stroke (AIS) caused by large-vessel occlusion; however, incomplete microvascular reperfusion and blood–brain barrier (BBB) disruption frequently limit its clinical benefit. Emerging evidence implicates neutrophil-driven thrombo-inflammation, particularly neutrophil extracellular trap (NET)–mediated microvascular obstruction, as a key mechanism underlying post-reperfusion hypoperfusion and secondary neurovascular injury. Colchicine, an FDA-approved microtubule inhibitor, potently suppresses neutrophil effector functions with a favorable safety profile, making it a promising adjunct to ischemia–reperfusion.&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;Using a transient middle cerebral artery occlusion (tMCAO) mouse model of ischemia–reperfusion, colchicine (0.8 mg/kg, intraperitoneal) was administered at reperfusion. We assessed circulating neutrophil response and activation, neutrophil F-actin polymerization, NET formation, microvascular fibrin(ogen) deposition, cerebral blood flow, leukocyte brain infiltration, BBB integrity, and neuroinflammation at acute and subacute time points. Whole-blood phagocytosis and bone marrow cellularity were examined at Day 3 after tMCAO. Neutrophil depletion was achieved using an anti-Ly6G antibody. Long-term neurological outcomes and brain tissue loss were evaluated up to 14 days after tMCAO.&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;Colchicine administration at reperfusion significantly blunted early neutrophil increase and activation, inhibited neutrophil F-actin polymerization, and suppressed intravascular NET formation and microvascular fibrin(ogen) deposition in tMCAO mice. It also improved cerebral blood flow, reduced leukocyte brain infiltration, attenuated BBB disruption, and decreased infarct size. Importantly, colchicine-treated mice exhibited sustained improvements in sensorimotor and cognitive function and reduced chronic brain tissue loss. Notably, colchicine did not exacerbate post-stroke immunosuppression, and its neuroprotective effects were abolished by neutrophil depletion.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Colchicine administered at reperfusion suppresses neutrophil-driven thrombo-inflammation, preserves BBB integrity, and improves cerebral blood flow, resulting in reduced ischemic brain injury and long-term neurological deficits after ischemic stroke. These findings suggest colchicine might be developed as a potential adjunctive therapy to limit reperfusion","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417141","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":"Sodium Butyrate Attenuates Sevoflurane-Induced Impaired Myelination and Neurobehavioral Deficits in Neonatal Mice via the H3K9ac/BDNF/TrkB Pathway","authors":"Chang Liu,&nbsp;Xinyao Bai,&nbsp;Xinyue Liu,&nbsp;Jinjie Li,&nbsp;Ruizhu Liu,&nbsp;Jinlan Jiang,&nbsp;Guoqing Zhao","doi":"10.1002/cns.71026","DOIUrl":"10.1002/cns.71026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early-life exposure to sevoflurane is considered an important risk factor for abnormal neurodevelopment and may lead to impaired myelination and neurobehavioral deficits in neonatal mice. Sodium butyrate (NaB), a short-chain fatty acid (SCFA) with epigenetic regulatory activity, has shown neuroprotective effects in various neurological disorders. However, the role of NaB in sevoflurane-induced myelination impairment and the underlying molecular mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An in vivo neonatal mouse model of sevoflurane exposure was established to investigate its effects on myelination and neurobehavioral function. NaB intervention was then administered to evaluate its potential to ameliorate sevoflurane-induced myelination impairment and neurobehavioral deficits. In vitro, human oligodendrocyte precursor cells (HOPCs) were directly treated with different concentrations of NaB to examine its effects on cell proliferation, migration, differentiation, and related molecular signaling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Repeated exposure to sevoflurane during the critical period of brain development in neonatal mice inhibited the proliferation and differentiation of oligodendrocyte precursor cells (OPCs), impaired myelination, and led to neurobehavioral deficits. NaB intervention ameliorated sevoflurane-induced myelination impairment and neurobehavioral dysfunction by regulating histone H3 lysine 9 acetylation (H3K9ac), upregulating brain-derived neurotrophic factor (BDNF) expression, promoting tropomyosin receptor kinase B (TrkB) phosphorylation, and increasing phosphorylated TrkB (p-TrkB) levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Repeated sevoflurane exposure in neonatal mice inhibited OPC proliferation and differentiation, impaired myelination, and caused neurobehavioral deficits. NaB ameliorated these impairments by regulating H3K9ac modification and increasing BDNF and p-TrkB levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409781","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":"Preoperative Plasma and Cerebrospinal Fluid SNAP-25 Levels Predict Delayed Neurocognitive Recovery in Elderly Patients: A Prospective Observational Study","authors":"Xiao-Yu Dou,&nbsp;Jing-Yu Li,&nbsp;Yi Qiu,&nbsp;Meng-Ying Xu,&nbsp;Hai-Yun Dong,&nbsp;Jiao Xue,&nbsp;Peng-Lei Ma,&nbsp;Min An","doi":"10.1002/cns.71028","DOIUrl":"10.1002/cns.71028","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;Delayed neurocognitive recovery (DNR) is a common postoperative complication in elderly patients, and its prevention and treatment remain challenging. Synaptosomal-associated protein 25 (SNAP-25), a potential biomarker for several neurodegenerative diseases, has been reported to be associated with the occurrence of DNR. However, whether SNAP-25 can predict the development of DNR remains unclear. Therefore, this study aimed to investigate the predictive value of preoperative SNAP-25 levels in cerebrospinal fluid (CSF) and plasma for DNR in elderly patients.&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;In this prospective observational study, elderly patients aged 65–75 years undergoing total knee arthroplasty under spinal anesthesia were enrolled. 3 mL of venous blood was collected upon entry into the operating room, and 1 mL of CSF was obtained after successful lumbar puncture and prior to intrathecal anesthetic injection. Neurocognitive function was assessed 1 day before surgery and 7 days after surgery. The primary outcome was the incidence of DNR. The predictors were preoperative CSF and plasma SNAP-25 levels. The association between SNAP-25 levels and DNR was further 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;A total of 86 patients completed the study, among whom 21 developed DNR, yielding an incidence of 24.4%. Preoperative SNAP-25 levels in both CSF and plasma were significantly lower in the DNR group than in the non-DNR group. Given the correlation between CSF and plasma SNAP-25 levels (&lt;i&gt;r&lt;/i&gt; = 0.89), two separate multivariable logistic regression models were constructed to avoid multicollinearity, higher SNAP-25 levels were associated with a reduced risk of DNR. ROC analysis showed that CSF SNAP-25 had an AUC of 0.805 (95% CI: 0.706–0.905), with an optimal cutoff value of 737.5 pg/mL (sensitivity: 0.905; specificity: 0.569), whereas plasma SNAP-25 had an AUC of 0.727 (95% CI: 0.618–0.837), with an optimal cutoff value of 543.5 pg/mL (sensitivity: 0.714; specificity: 0.708).&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;Preoperative SNAP-25 in both CSF and plasma is associated with DNR; although CSF SNAP-25 shows better discrimination, plasma SNAP-25 offers more balanced performance and greater clinical feasibility as a practical biomarker for identifying at-risk patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Trial Registration&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ChiCTR2500113164&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409775","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":"Olfml3 Regulates Microglial Inflammation and Neuronal Injury in Obstructive Sleep Apnea via Cybb-Mediated TLR4/NF-κB Pathway","authors":"Deqiu Kong,&nbsp;Yaowen Wang,&nbsp;Xianjun Chen,&nbsp;Cihao Hu,&nbsp;Bin Zhang,&nbsp;Xing Chen","doi":"10.1002/cns.71006","DOIUrl":"10.1002/cns.71006","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;Neurocognitive impairment in obstructive sleep apnea (OSA) is primarily driven by intermittent hypoxia (IH)-triggered neuroinflammation, where microglia play a pivotal role. The involvement of Olfml3 in IH-induced neuroinflammation remains unclear.&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;Single-cell RNA sequencing (scRNA-seq) data from the hippocampi of IH-induced OSA mice were analyzed to identify cell subpopulations, with further focus on Olfml3's differential expression, enriched pathways, and differentiation trajectories in microglia. An in vitro OSA model was established using IH-treated microglia. qRT-PCR and western blot (WB) were utilized to assess Olfml3 and cytochrome b (Cybb) expression. Microglial polarization was evaluated via flow cytometry, while Enzyme-Linked Immunosorbent Assay (ELISA) was applied to quantify inflammatory cytokines. Reactive oxygen species (ROS) were detected using fluorescent probes, and TLR4/NF-κB pathway activation was verified by WB assessment of Toll-like receptor 4 (TLR4), phosphorylated-p65 (p-p65), and p65 expression. Neuronal injury was assessed by treating neurons with microglial-conditioned medium, followed by CCK-8 for viability assessment and flow cytometry for apoptosis analysis. An in vivo OSA model was constructed by exposing mice to IH treatment. Cognitive deficits of mice were evaluated using the Morris water maze and blood oxygen saturation measurement, while pathological changes in brain tissue and cell apoptosis were examined via HE and TUNEL staining. Immunohistochemistry staining was employed to detect Olfml3 and Cybb protein levels. An immunofluorescence assay was conducted to measure Iba1 for evaluating microglial activation. ROS levels were detected by using fluorescent probes. The expression of TLR4/NF-κB pathway proteins was assessed by WB. CD86/CD206 ratios were analyzed by flow cytometry, and the expression of inflammatory cytokines was analyzed by ELISA.&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;scRNA-seq revealed reduced microglial proportions under hypoxia, with further analysis revealing that Olfml3 in microglia had a negative correlation with Cybb. An IH-induced OSA model confirmed that Olfml3 overexpression alleviated microglial inflammation and neuronal injury by suppressing the TLR4/NF-κB pathway via Cybb. In vivo experiments further validated Olfml3's protective role against IH-induced neuroinflammation in OSA.&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;Olfml3 in microglia mitigates IH-induced proinflammatory activation a","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409752","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 Protective Mechanism of Continuous Theta Burst Stimulation in the Acute Phase of Stroke Through Modulation of the Calcineurin/AKT/FOXO1 Signaling Pathway","authors":"Pengkun Yang,&nbsp;Haocheng Qin,&nbsp;Bao Zhou,&nbsp;Shenyi Kuang,&nbsp;Meixi Liu,&nbsp;Yi Wu,&nbsp;Peng Yuan,&nbsp;Kewei Yu","doi":"10.1002/cns.71017","DOIUrl":"10.1002/cns.71017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the neuroprotective effects of continuous theta-burst stimulation (cTBS) during the acute phase of ischemic stroke and its impact on neuronal apoptosis in the peri-infarct region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MCAO was induced in mice using the Longa method. cTBS was administered daily for seven days. Motor function and limb coordination were assessed behaviorally. Transcriptomic and proteomic analyses of the peri-infarct region were performed to explore mechanisms. Immunofluorescence and Western blot analyzed key proteins in the calcineurin/AKT/FOXO1 pathway, while TUNEL staining assessed neuronal apoptosis. AAV-mediated gene knockdown was used to validate the pathway's role in apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>cTBS improved motor performance, reduced infarct volume, and preserved peri-infarct tissue architecture. It suppressed calcineurin expression, enhanced calcineurin/AKT/FOXO1 pathway activation, and decreased neuronal apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>cTBS exerts neuroprotection by modulating the calcineurin/AKT/FOXO1 pathway, ultimately inhibiting neuronal apoptosis in the peri-infarct region.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403003","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":"Loss of Function of AFG3L2 Leading to Developmental and Epileptic Encephalopathy","authors":"Zou Pan,&nbsp;Li Yang,&nbsp;Haiyan Tang,&nbsp;Chen Chen,&nbsp;Qian Yang,&nbsp;Tenghui Wu,&nbsp;Fang He,&nbsp;Zhanwei Zhang,&nbsp;Fangyun Liu,&nbsp;Jing Peng","doi":"10.1002/cns.71013","DOIUrl":"10.1002/cns.71013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To delineate the clinical features of <i>AFG3L2</i>-related developmental and epileptic encephalopathy (DEE) and explore its pathogenic mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-genome and blood transcriptome sequencing were performed in undiagnosed DEE patients. Patient-derived skin fibroblasts were established for the analysis of RNA and protein expression as well as for mitochondrial functional assays, including OPA1 processing, mtDNA copy number, membrane potential, ATP production, mitochondrial morphology analysis, and mitochondrial stress testing. Additionally, published <i>AFG3L2</i>-related epilepsy cases were systematically reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified four novel <i>AFG3L2</i> variants in four DEE patients from two unrelated families, including splice-site/intronic variants in one family and exon-deletion/intronic variants in the other, fitting a recessive model of disease. In these patients, plus six additional previously reported DEE patients, symptoms included severe developmental delay, intractable seizures, microcephaly, generalized spasticity, and progressive cerebral atrophy. Transcriptome and fibroblast functional analyses revealed aberrant splicing, reduced <i>AFG3L2</i> expression, defective OPA1 processing, decreased mtDNA content, impaired membrane potential and ATP production, fragmented mitochondrial networks, and diminished respiratory capacity, supporting a loss-of-function mechanism. Compared with spastic ataxia 5—usually involving null-missense or missense-missense genotypes—DEE predominantly features null-null combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>We implicate <i>AFG3L2</i> as a novel causative gene for DEE, likely through mitochondrial proteostasis failure and bioenergetic compromise, expanding the phenotypic and genotypic spectrum of <i>AFG3L2</i>-related disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395251","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":"Potential Mechanisms of Trimetazidine and Coenzyme Q10 Against Antipsychotic-Induced Myocarditis: A Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Study","authors":"Ximing Chen,&nbsp;Dongyin Zhuo,&nbsp;Jiatong Zou,&nbsp;Haitao Song,&nbsp;Kaifang Yao,&nbsp;Hongjun Tian,&nbsp;Chuanjun Zhuo","doi":"10.1002/cns.71009","DOIUrl":"10.1002/cns.71009","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;Antipsychotic-induced myocarditis is a rare but potentially fatal adverse event associated with antipsychotic treatment. Trimetazidine (TMZ) and coenzyme Q10 (CoQ10) have shown potential cardioprotective effects. Thus, they may represent adjunctive therapeutic candidates for antipsychotic-induced myocarditis. However, the underlying molecular mechanisms and therapeutic relevance of this remain unclear. This study aimed to identify the potential pharmacological mechanisms and therapeutic targets of TMZ and CoQ10 in antipsychotic-induced myocarditis.&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;Drug- and disease-associated targets were retrieved or predicted using SwissTargetPrediction, SEA, PharmMapper, Super-PRED, and GeneCards. Overlapping drug-disease targets were identified and used to construct a protein–protein interaction network and determine the core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed using DAVID. Finally, molecular docking and molecular dynamics simulations were conducted to evaluate ligand-target interactions and the stability of the selected complexes.&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;Twenty-six overlapping TMZ-disease targets and 27 overlapping CoQ10-disease targets were identified. GO and KEGG enrichment analyses revealed that these targets were involved in multiple biological processes, cellular components, molecular functions, and signaling pathways. Thirty-nine unique drug-disease intersection targets were obtained after merging the TMZ-disease and CoQ10-disease targets and five core targets were identified: STAT3, NFKB1, HIF1A, CASP3, and MMP9. Further GO and KEGG enrichment analyses were conducted for the 39 drug-disease intersection targets. GO enrichment analysis indicated that the apoptotic process was greatly enriched, whereas KEGG analysis highlighted the PI3K/AKT signaling pathway. Molecular docking suggested that TMZ and CoQ10 could form stable interactions with the core targets, supporting their potential therapeutic relevance. The molecular dynamics simulations further supported the stability of the selected ligand-target complexes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Network pharmacology, molecular docking, and molecular dynamics simulations were used to investigate the potential pharmacological mechanisms underlying the effects of TMZ and CoQ10 in antipsychotic-induced myocarditis. The findings provide theoretical and computational evidence for future experimental studie","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389780","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}