CNS Neuroscience & Therapeutics最新文献

{"title":"Elucidating Trigonelline's Therapeutic Mechanisms for Traumatic Brain Injury Through Integrated Network Pharmacology and In Vivo Validation.","authors":"Qian Zhang, Yuefan Zhang, Zhibing Song, Zixiang Tang, Guoqiang Wang, Xiang Yang, Jincai Li, Tiejun Li","doi":"10.1002/cns.70803","DOIUrl":"10.1002/cns.70803","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) triggers complex pathological cascades, including inflammation, oxidative stress, apoptosis, and gliosis, particularly during the acute phase after injury. Trigonelline has been reported to exert neuroprotective effects in experimental models; however, its molecular mechanisms in acute TBI remain insufficiently defined.</p><p><strong>Objective: </strong>This study aimed to elucidate the molecular targets and mechanisms by which trigonelline attenuates acute TBI using an integrated network pharmacology and experimental validation approach.</p><p><strong>Methods: </strong>A trigonelline-target interaction network was constructed based on network pharmacology, followed by GO/KEGG analyses to predict the biological processes and pathways involved. Molecular docking was conducted to validate the binding affinity of trigonelline with key targets. Animal experiments were carried out to confirm the mechanistic predictions.</p><p><strong>Results: </strong>Network pharmacology identified GAPDH, IL6, ALB, TNF, and IL1B as major hub genes associated with trigonelline. GO/KEGG analyses suggested that the neuroprotective effects of trigonelline against TBI primarily involved the MAPK and PI3K-Akt pathways. In vivo assays demonstrated that trigonelline treatment significantly reduced brain water content, inflammation, and oxidative stress levels within 72 h post-injury, while ameliorating histopathological damage, as confirmed by ELISA, HE, and LFB staining. TUNEL, NeuN, and FJB staining further revealed that trigonelline attenuated TBI-induced neuronal apoptosis. Western blotting demonstrated that trigonelline suppressed MMP-9 and AQP4 expression and attenuated the triggering of the MAPK signaling pathway.</p><p><strong>Conclusion: </strong>By attenuating MAPK signaling and apoptosis, trigonelline mitigates neural damage following TBI. The present findings provide experimental evidence supporting the neuroprotective effects of trigonelline in an acute TBI model.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":"e70803"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12970217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375491","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":"Midkine Overexpression Promotes Functional Recovery After Spinal Cord Injury by Enhancing Microglial Efferocytosis Via LRP-1.","authors":"Yu Wang, Lu Fang, Chenyuan Zhai, Jili Cai, Xiangzhe Li, Lijuan Zong, Yao Geng, Chenchen Zhu, Cheng Sun, Manyu Dong, Yilun Qian, Yan Liu, Ying Huang, Zun Wang, Tong Wang, Wen-Tao Liu, Qi Wu","doi":"10.1002/cns.70841","DOIUrl":"10.1002/cns.70841","url":null,"abstract":"<p><strong>Objective: </strong>Traumatic spinal cord injury (SCI) induces neuronal apoptosis and neuroinflammation, which exacerbate secondary damage and hinder functional recovery. Efficient clearance of apoptotic cells and modulation of the inflammatory microenvironment of spinal cord are essential for promoting tissue repair. This study aimed to investigate whether Midkine (MDK), a heparin-binding growth factor, facilitates functional recovery after SCI and explores the underlying mechanisms.</p><p><strong>Methods: </strong>A rat model of moderate SCI was established using Allen's impact method. Lentiviral vectors were used to overexpress MDK in the spinal cord. Behavioral assessments, including BBB score and gait analysis, were performed to evaluate motor function recovery. Motor evoked potentials (MEPs) serve as a neurophysiological tool for evaluating the functional integrity of the corticospinal tract. In vivo and in vitro experiments were conducted to assess microglial efferocytosis and elucidate the underlying molecular mechanisms.</p><p><strong>Results: </strong>Transcriptomic bioinformatic analysis suggests that SCI is characterized by pronounced accumulation of apoptotic cells and robust neuroinflammatory responses, whereas single-cell analysis implicates MDK as a key contributor to neurorepair after SCI. MDK expression is dynamically regulated following SCI, with an early upregulation followed by a gradual decline over time, its location predominantly observed around microglial cells. Functionally, MDK overexpression significantly enhances motor recovery after SCI, accompanied by reduced neuroinflammation, decreased neuronal apoptosis, and improved neuroprotection. Mechanistically, MDK promotes microglial efferocytosis both in vivo and in vitro, activates the AKT/mTOR signaling pathway, upregulates BDNF and LRP-1 expression, and facilitates microglial polarization toward an anti-inflammatory M2 phenotype. Notably, inhibition of LRP-1 with receptor-associated protein (RAP) abolished the efferocytic and neuroprotective effects of recombinant MDK, highlighting LRP-1 as a key mediator of MDK's actions in microglia.</p><p><strong>Conclusion: </strong>Our study unveils the MDK/LRP-1/efferocytosis axis as a previously unrecognized therapeutic target for SCI. By orchestrating apoptotic cell clearance, dampening neuroinflammation, and fostering neuroprotection, this axis critically shapes the post-injury microenvironment to facilitate recovery. These findings suggest that MDK-centered therapy may represent a strategy for spinal cord repair, with LRP-1 modulation offering precise control over microglial responses.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":"e70841"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483937","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":"Cell-Type-Specific WTAP and ALKBH5-Mediated m⁶A Methylation Orchestrates Mental Disorders via Gut-Brain Axis Metabolite Signaling: Multi-Omics Evidence and Pyroptosis-Associated Loop Mechanism.","authors":"Jingjing Zhang, Xue Liu, Xiaoming Liu, Liqun Zhao, Junjie Bi","doi":"10.1002/cns.70840","DOIUrl":"10.1002/cns.70840","url":null,"abstract":"<p><strong>Introduction: </strong>Mental disorders affect one billion people and contribute 5% of global DALYs. Although N6-methyladenosine (m⁶A) modification, gut microbiota, cerebrospinal fluid (CSF) metabolites, and pyroptosis have been implicated in disease pathogenesis, the directionality and magnitude of causal links remain elusive. We integrated two-sample Mendelian randomization (MR) with single-cell eQTL data to generate hypotheses regarding these relationships.</p><p><strong>Methods: </strong>Using large-scale GWAS summary statistics, we estimated the causal effects of m⁶A regulators, gut microbiota, CSF metabolites, and pyroptosis on depression, schizophrenia (SZ), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Mediation analysis quantified hypothesized microbiota- and metabolite-mediated proportions; single-cell eQTL from 14 immune subsets localized genetic associations to cell types.</p><p><strong>Results: </strong>MR analysis suggested distinct causal associations of m⁶A modifiers (WTAP/ALKBH5) with mental disorders. Gut microbiota (e.g., GCA-900066755, Bacillus) and CSF metabolites (e.g., theophylline, isoleucine) were estimated to potentially mediate 5.06%-45.28% of these effects, forming pathways such as WTAP → GCA-900066755 → theophylline → ADHD and ALKBH5 → CAG-390 → isoleucine → PTSD. These represent statistically inferred associations rather than experimentally validated pathways. Notably, these proportions were not based on multiple-testing-corrected associations. Single-cell eQTL mapping associated WTAP's ADHD risk with XCL1-NK cells (OR = 1.445). Bidirectional MR suggested potential reciprocal associations between mental disorders and microbial/metabolite profiles. Pyroptosis demonstrated a tentative statistical association (3.99% explanatory power), though its specific biological role remains undefined.</p><p><strong>Conclusion: </strong>This multi-omics integration generates a hypothesis regarding a potential m⁶A-microbiota-metabolite axis that may be associated with mental disorders, with pyroptosis as a potentially related peripheral factor. Should these associations prove causal, the identified relationships could suggest peripheral intervention nodes, while combinatorial targeting might provide directions for preventive psychiatry. Experimental validation is required to confirm the biological mechanisms implied by these genetic associations.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":"e70840"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Critical Four-Hour Therapeutic Window Predicts Delayed Encephalopathy Risk After Carbon Monoxide Poisoning: A Multicenter Retrospective Cohort Study.","authors":"Shaokun Wang, Yanxia Gao, Jie Ran, Yan Zhang, Yanling Chen, Hongyi Yan, Li Pang","doi":"10.1002/cns.70837","DOIUrl":"10.1002/cns.70837","url":null,"abstract":"<p><strong>Aims: </strong>The therapeutic window for preventing delayed encephalopathy after carbon monoxide poisoning (DEACMP) remains unclear. We aimed to define this temporal risk relationship and establish an intervention threshold using machine learning.</p><p><strong>Methods: </strong>In this multicenter retrospective cohort study (n = 1755), a gradient boosting model for predicting DEACMP was developed (n = 1654) and externally validated (n = 101). Performance was assessed using the area under the receiver operating characteristic curve (AUC) and interpreted using Shapley Additive exPlanations (SHAP).</p><p><strong>Results: </strong>The exposure-to-treatment interval was the most powerful predictor of DEACMP risk. Intervention within four hours emerged as the most critical variable influencing risk (SHAP analysis). The model demonstrated robust discrimination in the training (AUC = 0.944, 95% CI, 0.926-0.960), internal validation (AUC = 0.849, 95% CI, 0.785-0.905), and external validation (AUC = 0.872, 95% CI, 0.772-0.946) sets.</p><p><strong>Conclusion: </strong>Treatment delay is the primary modifiable risk factor for DEACMP following CO poisoning. The identified critical four-hour therapeutic window provides the first quantitative, evidence-based benchmark to inform clinical guidelines and optimize emergency response strategies aimed at preventing delayed neurological sequelae.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":"e70837"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490262","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 Real-World Safety Profile of Temazepam: A 20-Year Pharmacovigilance Analysis Based on the Large-Scale FAERS Database.","authors":"Zujun Wen, Xiang Liu, Peng Liu","doi":"10.1002/cns.70836","DOIUrl":"10.1002/cns.70836","url":null,"abstract":"<p><strong>Objective: </strong>Temazepam has not been adequately investigated for its long-term safety profile in broad patient populations. This study aimed to characterize temazepam's real-world long-term safety profile.</p><p><strong>Methods: </strong>Reports of adverse events from Q1 2006 to Q4 2025 comprising temazepam were collected from the FAERS database. Data were analyzed using disproportionality methods including the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the multi-item gamma poisson shrinker (MGPS), and the Bayesian confidence propagation neural network (BCPNN).</p><p><strong>Results: </strong>A total of 2788 adverse event reports associated with temazepam were retrieved. The most frequently reported events were drug ineffective, eye irritation, and toxicity to various agents. We also detected numerous ocular risk signals absent from the product label, together with potential abuse signals. Furthermore, our study identified several behavioral risk signals such as abnormal behavior, aggression, and amnesia and parasomnias-related adverse events like nightmare and somnambulism.</p><p><strong>Conclusions: </strong>A comprehensive analysis of the large scale real world FAERS database was performed in this study identifying an extensive spectrum of adverse events associated with temazepam. Our study confirmed established risks and detected potential novel signals including ocular toxicities (e.g., eye irritation, intraocular pressure increased, glaucoma, eye inflammation, and photophobia) as well as neuro behavioral adverse outcomes such as aggression, amnesia and parasomnias (e.g., nightmare and somnambulism). These findings provide compelling support for temazepam clinical monitoring and risk assessment.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":"e70836"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497006","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":"Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis","authors":"Shihui Guo,&nbsp;Weishan Fu,&nbsp;Yating Wang,&nbsp;Qi Liu,&nbsp;Jiaxin Li,&nbsp;Kai Guo,&nbsp;Hongsheng Zhang","doi":"10.1002/cns.70807","DOIUrl":"10.1002/cns.70807","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD), the most common form of dementia, lacks effective disease-modifying treatments. Rapamycin, an mTOR inhibitor with immunomodulatory properties, may mitigate AD pathology by restoring microglial functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rapamycin was orally administered to 2-month-old 5xFAD and hAPP^NL-G-F mice (amyloid plaque-dominant AD models). At 5 months of age, these mice were subjected to behavioral, histopathological, and molecular analyses. To assess microglial function, primary microglia were treated with rapamycin and evaluated for their ability to phagocytose and degrade fluorescently labeled amyloid-β (Aβ) via the IncuCyte real-time imaging system. Furthermore, the effects of rapamycin and autophagy inhibitors on lipid droplet content were analyzed in oleic acid-treated BV2 microglial cells using flow cytometry and confocal microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Rapamycin treatment reduced the cerebral Aβ plaque burden, alleviated dystrophic neurites, suppressed glial hyperactivation, and increased plaque-associated microglial density in both mouse models, with more pronounced effects in female mice. These pathological improvements were associated with attenuated deficits in hippocampal-dependent memory tasks (spontaneous alternation in the Y-maze and contextual fear conditioning tasks). Mechanistically, rapamycin enhances microglial lysosomal degradation, promotes lipid droplet clearance in BV2 cells, and increases Aβ phagocytic clearance in primary microglial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that rapamycin reduces amyloid pathology and associated behavioral deficits in AD mice, an effect associated with enhanced microglial lysosomal activity and Aβ clearance, highlighting its therapeutic potential in AD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Renal Dysfunction and Cerebral Small Vessel Disease: A Prospective Cohort Study From the UK Biobank","authors":"Xiaowei Sun,&nbsp;Jiawen Chen,&nbsp;Yang Gao,&nbsp;Yingjie Chen,&nbsp;Yan Li,&nbsp;Rui Pang,&nbsp;Ling Cai,&nbsp;Zhangsheng Yu,&nbsp;Dan Huang,&nbsp;Peiying Li","doi":"10.1002/cns.70802","DOIUrl":"10.1002/cns.70802","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to test the association between multidimensional renal dysfunction biomarkers and cerebral small vessel disease (CSVD) risk using data from the UK Biobank.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present study encompasses two cohorts. The whole cohort consisted of 43,314 adults without neurological diseases at baseline, who underwent brain magnetic resonance imaging (MRI) during the follow-up period. CSVD imaging markers, including white matter hyperintensity (WMH) volume, mean diffusivity (MD), and fractional anisotropy (FA), were extracted. The sub-cohort consisted of 9786 adults randomly selected from the whole cohort. CSVD MRI features, including the presence of lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs), as well as CSVD burden score, were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the whole cohort, renal dysfunction as reflected by abnormalities in estimated glomerular filtration rates and blood urea nitrogen was associated with increased WMH and MD values and decreased FA values, compared to the healthy group. We observed consistent findings in the sub-cohort: multidimensional renal dysfunction was associated with increased risk of lacunes, WMHs, EPVS, and CMBs, as well as greater severity of CSVD burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our large-scale epidemiological study provides evidence that multidimensional renal dysfunction biomarkers are independently associated with CSVD risk in adults.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12930275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275329","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":"Oxygen Therapy for Intracranial Hemorrhage","authors":"Qiqi Shi,&nbsp;Song Han,&nbsp;Xiangyu Li,&nbsp;Jingwei Guan,&nbsp;Yanli Duan,&nbsp;Zhangyuan Liao,&nbsp;Zhiying Chen,&nbsp;Weili Li,&nbsp;Ran Meng,&nbsp;Ming Zou,&nbsp;Jiayue Ding","doi":"10.1002/cns.70806","DOIUrl":"10.1002/cns.70806","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Intracranial hemorrhage (ICH) is a severe cerebrovascular disease with a high mortality rate that impairs patient well-being and quality of life. Oxygen therapies, including hyperbaric hyperoxia (HBO) and normobaric hyperoxia (NBO), have attracted widespread attention as potential adjuvant treatments because of their neuroprotective effects. This review aimed to summarize the current literature addressing the neuroprotective mechanisms of oxygen therapy in ICH, as well as its effectiveness and safety in patients with ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically searched multiple literature databases including PubMed, Embase, and Cochrane for publications containing specified keywords and published prior to November 2025. The references were thoroughly reviewed to identify other articles that may have been missed in our search.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 38 articles were included in this study. Among them, 20 mainly studied the mechanism of oxygen therapy after ICH, eight mainly investigated the effects of oxygen therapy in patients with ICH, and 10 primarily analyzed the safety of oxygen therapy in patients with ICH. The experimental results showed that the treatment mechanism of HBO mainly involves reducing cerebral vasospasm, promoting angiogenesis, inhibiting inflammatory responses, and improving aerobic energy metabolism, whereas NBO mainly protects the blood–brain barrier (BBB), reduces cerebral edema and hemispheric swelling, mitigates acute inflammation, inhibits oxidative stress and neuronal cell death, and enhances aerobic metabolism. Clinical trials have shown that oxygen therapy can improve neurological function recovery and long-term prognosis in patients with ICH, as reflected by better scores in some indicators and lower mortality rates; however, oxygen therapy also has controversial and potential risks. Excessive oxygen supply may lead to adverse reactions, and hyperoxia may negatively impact patients with ICH. An appropriate treatment plan should be formulated for the clinical application of oxygen therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Oxygen therapy shows potential in ICH treatment through multiple mechanisms; however, its safety and optimal regimen require further large-scale randomized controlled trials to balance the benefits and risks and optimize its application strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281422","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":"Chidamide Is Screened to Suppress Epileptogenesis in Mice Models via Blocking Histone Deacetylase 1","authors":"Qian Guo,&nbsp;Zhao-Jun Wang,&nbsp;Wei-Bo Dong,&nbsp;Li Pang,&nbsp;Xiao-Yuan Mao","doi":"10.1002/cns.70805","DOIUrl":"10.1002/cns.70805","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Disease-modifying and anti-epileptogenic therapies for epilepsy remain limited. Given the critical role of histone deacetylases (HDACs) in epileptogenesis, this study aimed to identify effective HDAC inhibitors and evaluate their anti-epileptogenic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A Mg²⁺-free neuron-like PC12 cell model was used to screen FDA-approved HDAC inhibitors in vitro. Acute and chronic epilepsy models were induced in mice using pentylenetetrazol (PTZ) or kainic acid (KA). Spontaneous recurrent seizures (SRS) were monitored by electroencephalogram (EEG). Neuronal survival, mossy fiber sprouting (MFS), and glial activation were assessed by Nissl staining, Timm staining, and immunofluorescence, respectively. HDAC1 expression was analyzed by Western blot and immunofluorescence. Neuron-specific HDAC1 overexpression was achieved using adeno-associated virus (AAV2; hereafter referred to as AAV)-mediated gene transfer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chidamide (Chi) exhibited the most inhibitory effect among nine HDAC inhibitors. Chi significantly reduced seizure susceptibility in acute PTZ- and KA-induced models. In the chronic KA model, Chi attenuated SRS, improved neuronal survival, reduced MFS, and suppressed astrocytic and microglial activation. Chi markedly decreased hippocampal HDAC1 expression, while neuronal HDAC1 overexpression abolished its anti-epileptogenic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chi attenuates epileptogenesis by inhibiting neuronal HDAC1 and may serve as a promising repurposed anti-epileptogenic therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269317","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":"Linking Cortical Morphometry in Self-Limited Epilepsy With Centrotemporal Spikes to Cognition, Function, and Molecular Architecture","authors":"Siqi Yang,&nbsp;Jie Xia,&nbsp;Wei Liao,&nbsp;Yimin Zhou,&nbsp;Chengzong Peng,&nbsp;Juan Wang,&nbsp;Zhiqiang Zhang","doi":"10.1002/cns.70794","DOIUrl":"10.1002/cns.70794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Self-limiting epilepsy with centrotemporal spikes (SeLECTS) is the most common type of pediatric epilepsy, characterized by age-dependent seizures, which usually occur during the development of a child's brain. This condition is associated with heterogeneous neurodevelopmental alterations, including cortical thinning, changes in subcortical structures, and atypical development linked to the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To establish an integrative model of neurodevelopment in SeLECTS, we investigated how its structural brain alterations are linked to clinical phenotypes, aberrant brain network function, and the local molecular architecture. Using normative modeling, we analyzed magnetic resonance imaging (MRI)-derived morphometric features, specifically cortical thickness and subcortical volumes, in a multicenter preschool cohort (devCCNP, <i>n</i> = 457) and a SeLECTS cohort (<i>n</i> = 187) and generated deviation matrices specific to SeLECTS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nonnegative matrix factorization was applied to decompose these matrices into eight deviation components, revealing biologically interpretable patterns of heterogeneity, along with subject-specific loadings that quantify the expression of these components in individual subjects. Behavioral partial least squares analysis identified significant associations between subject-specific loadings and phenotypic profiles in SeLECTS, suggesting that factors such as age, medication history, and disease duration are important for morphological development—particularly in temporal and frontal regions associated with cognitive control and language. Furthermore, we explored the molecular basis of the morphometric deviation components by mapping their spatial expression to features related to functional cognition, neurotransmitter/transcript profiles, and mitochondrial characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, this study provides a novel framework for elucidating the neuroanatomical heterogeneity of epilepsy, offering insights into its behavioral and molecular correlates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269359","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}