Nan Wang, Baoshan Qiu, Weiqi Chen, Yuesong Pan, Yilong Wang
{"title":"Plasma Metabolites Link Non-Communicable Diseases to Increased White Matter Hyperintensities","authors":"Nan Wang, Baoshan Qiu, Weiqi Chen, Yuesong Pan, Yilong Wang","doi":"10.1111/cns.70507","DOIUrl":"https://doi.org/10.1111/cns.70507","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cerebral small vessel disease (CSVD) and non-communicable diseases (NCDs) are major global health burdens. White matter hyperintensities (WMH) are a key imaging feature of CSVD, but the relationship between WMH and NCDs, especially the role of plasma metabolites in this association, remains unclear. This study aims to elucidate this link.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included participants with WMH from the UK Biobank cohort and examined the prevalence of 29 common NCDs in this population. General linear regression was used to analyze the association between NCDs and WMH. Propensity score matching and elastic net regression identified plasma metabolites associated with NCDs. Mediation analysis was conducted to explore the role of these metabolites in the association between NCDs and WMH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 44,630 participants were included, of whom 47.0% were male. Approximately one-third of the participants had NCDs, with the most common being hypertension, dyslipidemia, and asthma. Compared to those without NCDs, the WMH volume in individuals with one or more comorbid NCDs was significantly increased by 18.43% to 68.15%. During a median follow-up of 9.5 years, individuals with hypertension, obstructive sleep apnea, and hypertension combined with coronary ischemic heart disease had significantly larger WMH volumes compared to those without NCDs, with increases of 30.81%, 36.44%, and 36.75%, respectively. Further analysis revealed that plasma metabolites associated with NCDs mediated this risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study elucidated the association between WMH and NCDs, showing that common NCDs significantly increase WMH volume. Plasma metabolites associated with NCDs mediate this risk. This provides new insights into preventing WMH progression in individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disrupted Glucose Metabolism Covariance Network in Amyotrophic Lateral Sclerosis","authors":"Xin Jin, Xueying Wang, Dingxin Zheng, Pubing Yuan, Jianyu Li, Ting Qiu, Huixiong Zhang, Yifan Chen, Jinfan Zhang, Feifei Wu, Qing Liu, Alessandro Grecucci, Yuanchao Zhang, Junling Wang, Xiaoping Yi, Lena Palaniyappan, B. Blair Braden","doi":"10.1111/cns.70537","DOIUrl":"https://doi.org/10.1111/cns.70537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to characterize the topological changes in glucose metabolism covariance networks in amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed the interregional coordination of <sup>18</sup>F-FDG-PET data to examine topological alterations in individualized glucose metabolism covariance networks in 127 ALS patients compared to 128 healthy controls (HC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to HC, ALS patients showed reduced small-worldness (lower normalized clustering coefficient, higher normalized characteristic path length) and decreased global and local efficiency, suggesting impaired global integration and local segregation. These network metrics correlated with disease progression and motor function. Regionally, altered degree centrality affected motor and default mode networks, and related to GABAa and mGluR5 receptor expression. Transcriptomic associations further linked these changes to immune function, synaptic signaling, and protein regulation. Bidirectional shifts in connectivity strength were observed, with both increased connectivity and disease progression independently predicting reduced survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings may provide valuable biomarkers for monitoring the progression of ALS and suggest potential mechanistic pathways for the development of innovative therapeutic strategies for this disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716977","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":"Assessment of the Impact of Statin Use to Predict All-Cause Mortality in Patients With Critical Cerebrovascular Disease: A Retrospective Cohort Study From the MIMIC-IV Database","authors":"Dong Tang, Zheng Huang, Shifu Li, Fenghua Chen","doi":"10.1111/cns.70542","DOIUrl":"https://doi.org/10.1111/cns.70542","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of statin therapy on short-term mortality among critically ill patients with hemorrhagic stroke or ischemic stroke remains uncertain. We investigated associations between statin use and ICU and hospital mortality in this patient population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study using the MIMIC-IV database, including 6918 patients (2960 HS and 3958 IS) after applying strict exclusion criteria. Statin use was assessed by type, dose (standard vs. high), and initiation timing (pre-ICU vs. post-ICU). Survival outcomes were evaluated using Kaplan–Meier analysis and multivariable Cox regression models, landmark analyses, and Fine–Gray competing-risk models, with propensity score matching to adjust for confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Statin use significantly reduced ICU mortality at 30 days in HS (HR = 0.59, 95% CI: 0.41–0.87) and IS (HR = 0.45, 95% CI: 0.32–0.64) cohorts. Atorvastatin and simvastatin showed pronounced protective effects, independent of dose intensity. Post-ICU initiation of statins conferred greater benefit compared with pre-ICU initiation, especially in HS patients. Shorter statin treatment duration (≥ 3 days) sufficiently captured beneficial effects. Patients with hyperlipidemia demonstrated enhanced mortality benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Statin use is associated with significantly lower short-term mortality in critically ill stroke patients, supporting tailored strategies for optimal statin initiation and duration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714671","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}
Yitong Du, Lin Wang, Ying Cui, Xiaojiao Xu, Mingkai Zhang, Yue Li, Ting Gao, Dan Gao, Zhi Sheng, Shiya Wang, Houzhen Tuo
{"title":"Effect of Probiotics Supplementation on REM Sleep Behavior Disorder and Motor Symptoms in Parkinson's Disease: A Pilot Study","authors":"Yitong Du, Lin Wang, Ying Cui, Xiaojiao Xu, Mingkai Zhang, Yue Li, Ting Gao, Dan Gao, Zhi Sheng, Shiya Wang, Houzhen Tuo","doi":"10.1111/cns.70541","DOIUrl":"https://doi.org/10.1111/cns.70541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) patients experience gut microbiota dysbiosis. Probiotic intervention could potentially serve as a safe and effective adjunctive therapeutic approach for PD, but its effects on rapid eye movement sleep behavior disorder (RBD) and motor symptoms in PD patients warrant further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To examine the influence of probiotics on RBD, motor symptoms, gut microbiota, and serum metabolites in individuals with PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this randomized controlled trial, PD patients were randomly allocated to either a probiotics or a control group while maintaining standard treatments. Clinical outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) and RBD Questionnaire-Hong Kong (RBDQ-HK) were assessed at baseline and post-treatment. Furthermore, fecal and blood samples were collected from PD patients at both timepoints, with additional samples obtained from healthy controls for comparison. The 16S rRNA gene V3-V4 region sequencing method was used to analyze gut microbiota composition, and untargeted metabolomic techniques were utilized to assess serum metabolite alterations, followed by correlation analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty eligible PD patients were enrolled and randomly allocated into two groups. After 12 weeks of intervention, the probiotic group showed significant reductions in both UPDRS total scores (−4.8 ± 7.5 vs. 1.8 ± 13.1, <i>p</i> = 0.009) and RBDQ-HK scores (−7.5 ± 6.5 vs. 0 ± 5.8, <i>p</i> = 0.015) compared to controls. Gut microbiota analysis revealed increased abundance of <i>Actinobacteria</i>, <i>Negativicutes</i>, and <i>Bacillus</i>, with reductions in <i>Lactococcus</i>, <i>Comamonas</i>, and <i>Enterococcus</i> after probiotic intervention. Furthermore, compared to normal controls, PD patients exhibited 9 significantly elevated and 11 significantly reduced metabolites; probiotic intervention altered the serum metabolome in PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrated probiotics' potential to ameliorate RBD and motor symptoms while positively affecting the composition of the gut microbiota and serum metabolites in PD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714672","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":"Albiflorin on Neuropsychiatric and Neurodegenerative Disorders: A Systematic Review","authors":"Shasha Sun, Hamizah Shahirah Hamezah, Chuanshan Jin, Rongchun Han, Xiaohui Tong","doi":"10.1111/cns.70535","DOIUrl":"https://doi.org/10.1111/cns.70535","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Albiflorin, a key compound from <i>Paeonia lactiflora</i>, has shown therapeutic potential in neuropsychiatric and neurodegenerative disorders (NPDs and NDDs), especially depression and Alzheimer's disease (AD). This review aimed to summarize its pharmacological effects, mechanisms, pharmacokinetics, and therapeutic prospects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Albiflorin exhibits multi-target actions, including modulation of monoamine neurotransmitters, inhibition of neuroinflammation, and enhancement of neuroplasticity. In AD, it reduces Aβ accumulation, improves mitochondrial function, and activates MAPK/ERK and Nrf2/HO-1 signaling pathways. In depression, it restores phospholipid and tryptophan metabolism, regulates HPA axis function, and increases BDNF expression. Albiflorin crosses the blood-brain barrier (BBB) and may act indirectly via the gut-brain axis through its metabolite benzoic acid. Though brain concentrations are low, its pharmacological effects remain significant. Albiflorin also shows potential benefits in conditions like cerebral ischemia and hypoxic-ischemic brain injury. Toxicological data indicate low systemic toxicity and good safety margins <i>in vivo</i> and <i>in vitro</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Albiflorin demonstrates promising therapeutic potential for NPDs and NDDs via multi-pathway regulation. However, further studies are needed to optimize brain delivery, understand gut microbiota interactions, and confirm efficacy through clinical trials. The advancement of formulation strategies and pharmacokinetic research will be considered key to achieving clinical translation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705659","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}
Guo-Jian Zhao, Li-Mei Zhang, Si-Rou Wang, Mei Yang, Jia-Hao Jiang, Bo-Xiang Yuan, Cheng Huang, Zhi-Hua Huang, Xiao-Lu Tang, Tao Chen
{"title":"AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through α7nAChR-ERK-STAT3 Signaling","authors":"Guo-Jian Zhao, Li-Mei Zhang, Si-Rou Wang, Mei Yang, Jia-Hao Jiang, Bo-Xiang Yuan, Cheng Huang, Zhi-Hua Huang, Xiao-Lu Tang, Tao Chen","doi":"10.1111/cns.70519","DOIUrl":"https://doi.org/10.1111/cns.70519","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroinflammation constitutes a critical pathological event subsequent to ischemic stroke. AD16, a novel anti-neuroinflammatory compound, has demonstrated efficacy in alleviating neuroinflammation in neonatal rats induced by ischemia–hypoxia. This study aims to elucidate the therapeutic utility and underlying mechanisms of AD16 in an adult ischemic stroke rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A rat transient middle cerebral artery occlusion (tMCAO) model was employed. Neurological function was evaluated using the Longa and Garcia JH scores, motor function was assessed through rotary rod and CatWalk gait analysis, and brain injury was examined via TTC and Nissl staining. Molecular docking techniques simulate the binding of a target compound to a potential target. Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to detect microglia phenotype, pro-inflammatory factors, and activation of signaling molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AD16 treatment improved neural function in tMCAO rats, reduced cerebral infarction volume and brain water content, preserved blood–brain barrier integrity, and inhibited pro-inflammatory cytokines. Molecular docking showed AD16 has high affinity for α7nAChR, TLR4, ERK, and STAT3. AD16 increased α7nAChR, CD206, and p-ERK protein levels, while decreasing CD40, CD68, TLR4, and p-STAT3. These effects were reversed by α-BTX (α7nAChR inhibitor) and U0126 (ERK inhibitor).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AD16 may inhibit microglia activation and polarization via the α7nAChR-ERK-STAT3 pathway, thus reducing neuroinflammation from cerebral ischemia and protecting the brain. This study suggests AD16 as a potential treatment for ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705360","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":"Sensory Afferent Neural Circuits Mediate Electroacupuncture to Improve Swallowing Function in a Post-Stroke Dysphagia Mouse Model","authors":"Yong Dai, Jiahui Hu, Qianqian Wang, Jia Qiao, Yueqin Tian, Chao Li, Jiemei Chen, Fei Zhao, Xinya Li, Chunyan Liu, Ruihuan Pan, Haining Ou, Nenggui Xu, Hongmei Wen, Zulin Dou, Qiuping Ye","doi":"10.1111/cns.70514","DOIUrl":"https://doi.org/10.1111/cns.70514","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Electroacupuncture (EA) has been reported to improve post-stroke dysphagia (PSD) effectively. However, the underlying afferent neural circuit and neurological mechanism involved in improving PSD remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A PSD mouse model was established via the photochemical embolization method. Laser scatter contrast imaging was used to evaluate blood perfusion. Videofluoroscopic swallowing study, flexible endoscopic evaluation swallowing, and electromyography were used to assess the swallowing function. Neuronal activities and neuron types were detected by immunofluorescence. Synaptic connections between the nucleus tractus solitarii (NTS), the ventral posteromedial thalamic nucleus (VPM), and the primary sensory cortex (S1) were verified by neural tracing. Finally, photogenetic, chemogenetic, and in vivo electromyography or electrophysiological records were used to explore the possible afferent neural circuits of EA therapy for PSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EA treatment potentiated the blood perfusion of CV23 and S1, improved the area under the curve, pharyngeal transit time, and vocal fold mobility in PSD model mice. EA also activated neuronal activities in VPM, while chemical genetic inhibition of VPM attenuated the swallowing function of EA enhanced in PSD mice. Neural tracing revealed the presence of direct synaptic connections in the neural circuit of NTS-VPM-S1, and excitatory neurons were the predominant type of synaptic projection. Activation of this circuit improved the swallowing function in PSD mice, whereas its inhibition impaired the swallowing function; this effect was reversible by EA-CV23.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings uncover the importance of sensory afferent neural circuits NTS-VPM-S1 in driving the protective effect of EA-CV23 against dysphagia and thus reveal a potential strategy for PSD intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705531","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}
Xiaoming Xin, Lei Miao, Lei Ci, Yun Wang, Zhiguo Zhang, Lingguo Meng, Jia Qi, Yicheng Mao, Yi-Zhun Zhu
{"title":"S-Propargyl-Cysteine Attenuates Stroke Heterogeneity via Promoting Protective Autophagy Across Multiple Neural Cell Types: Insights From Single-Cell Sequencing","authors":"Xiaoming Xin, Lei Miao, Lei Ci, Yun Wang, Zhiguo Zhang, Lingguo Meng, Jia Qi, Yicheng Mao, Yi-Zhun Zhu","doi":"10.1111/cns.70399","DOIUrl":"https://doi.org/10.1111/cns.70399","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Stroke, predominantly ischemic, is a leading cause of mortality and disability worldwide. Despite advances in intervention strategies, effective treatments to mitigate neurological injury post-ischemic stroke remain limited. Hydrogen sulfide (H<sub>2</sub>S), a gas signaling molecule, has been implicated in neuroprotection, but its role in stroke is controversial. S-propargyl-cysteine (SPRC), an H<sub>2</sub>S donor, has shown great potential in protecting against neurological injuries, but its mechanisms in ischemic stroke are not fully understood. This study investigates the neuroprotective potential of SPRC and its mechanisms, focusing on the interplay between H<sub>2</sub>S and autophagy in modulating the cerebral microenvironment post-stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive single-cell RNA sequencing analysis on ischemic brain tissue to elucidate the cellular heterogeneity and specific responses related to H<sub>2</sub>S synthesis and autophagy. We utilized the GEO repository dataset GSE174574, applying stringent filtering and batch effect correction using the Harmony R package. Cellular subpopulations were identified using established markers, and H<sub>2</sub>S and autophagy scores were calculated using the JASMINE package. We also measured serum H<sub>2</sub>S levels, evaluated the pharmacodynamics of SPRC in rats, and constructed a cerebral ischemia–reperfusion (I/R) injury model to assess the neuroprotective effects of SPRC. Additionally, we examined the role of SPRC in CBS and 3-MST knockout mice to determine the dependency on these H<sub>2</sub>S synthetases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed a dysregulation in the expression of H<sub>2</sub>S and autophagy-related genes in central nervous system cells, particularly in neurons, following stroke. SPRC administration significantly improved neurological behavior, metabolic activity, reduced brain infarction size, and ameliorated ultrastructure changes in stroke-affected rats. Interestingly, SPRC continued to provide neuroprotection even after the knockdown of CBS and 3-MST, indicating a CBS/3-MST-independent mechanism. Furthermore, SPRC preserved the endogenous H<sub>2</sub>S level and strongly upregulated protective autophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study is the first to reveal the neuroprotection of SPRC in cerebral I/R injury in a classical enzymatic CBS/3-MST independent manner. The potential cellular and molecular mechanisms may rely on ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688039","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":"Transcranial iTBS Combined With Trans-Spinal iTBS Targeting PDE1A/cAMP/PKA Axis Regulates Neural Regeneration After Spinal Cord Injury","authors":"Yingxue Fu, Xianbin Wang, Xingyu Chen, Shuang Wu","doi":"10.1111/cns.70525","DOIUrl":"https://doi.org/10.1111/cns.70525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the impact of intermittent theta burst stimulation (iTBS) treatment at various targets on spinal cord injury (SCI), as well as the effects of dual-target iTBS therapy on neurological functional recovery in rats with SCI and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using an improved Allen's method, an incomplete C6 SCI model was established. Postoperatively, the rats with SCI underwent transcranial iTBS, trans-spinal iTBS, or dual-target iTBS. Neurological functional recovery and synaptic function following SCI were evaluated through behavioral tests, footprint analysis, electrophysiological assessments, pathological staining, transmission electron microscopy, Golgi staining, and immunofluorescence staining. The expression of relevant proteins and genes was assessed using Western blotting and qRT-PCR. Proteomic and metabolomic sequencing analyses of spinal cord tissue from each group were conducted to investigate specific mechanisms. Additionally, lentivirus was used to infect primary neurons to elucidate the effect of PDE1A. Furthermore, lentivirus was applied to SCI rats to explore the influence of PDE1A on neurological and synaptic functions following SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with the single-target iTBS group, dual-target iTBS treatment significantly improved motor function and reduced the damaged area of the spinal cord in SCI rats. Following dual-target iTBS intervention, SCI rats exhibited improvements in neural function and synaptic function. Sequencing analysis identified the protein PDE1A present in all groups, and the protein interaction network revealed that PDE1A is involved in the cAMP signaling pathway, with an increase in PDE1A expression observed after SCI. Additionally, inhibiting PDE1A promoted the expression of cAMP and protein kinase cAMP-activated catalytic subunit alpha (PRKACA) in primary neurons, thereby facilitating synapse function in primary neurons. Inhibition of PDE1A also improved neural connection and synaptic reconstruction in SCI rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Compared with single-target iTBS treatment, dual-target iTBS treatment promotes the recovery of motor function and spinal cord tissue repair more effectively in SCI rats. Dual-target iTBS may promote neural regeneration and synaptic remodeling after SCI by regulating the PDE1A-cAMP-PKA signaling pathway, thereby improving neurological dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687894","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}
Dian-Wei Wu, Chang-Geng Song, Rong Chen, Jing-Jing Zhao, Ying-Chi Zhang, Xuan Wang, Zhong-Qing Sun, Xiao-Gang Kang, Qiong Gao, Wen Jiang
{"title":"Glymphatic Function as a Prognostic Biomarker in Prolonged Disorders of Consciousness","authors":"Dian-Wei Wu, Chang-Geng Song, Rong Chen, Jing-Jing Zhao, Ying-Chi Zhang, Xuan Wang, Zhong-Qing Sun, Xiao-Gang Kang, Qiong Gao, Wen Jiang","doi":"10.1111/cns.70526","DOIUrl":"https://doi.org/10.1111/cns.70526","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The glymphatic system is a major waste clearance system in the central nervous system. We aim to investigate the glymphatic function and its prognostic values in patients with prolonged disorders of consciousness (pDoC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective and explorative cohort study including 40 patients with pDoC and 20 healthy controls. Glymphatic function was measured with the global and regional blood-oxygen-level-dependent and cerebrospinal fluid (BOLD-CSF) couplings, characterized by time-lags and strengths of the couplings. The clinical outcome was defined as improvement and no improvement in consciousness 6 months after enrollment, determined via a structured telephone follow-up based on the Coma Recovery Scale-Revised (CRS-R) score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with pDoC exhibited significantly delayed time-lags in BOLD-CSF coupling (<i>p</i> < 0.05) and significantly reduced coupling strengths (<i>p <</i> 0.05) when compared to healthy controls. Follow-up studies indicated that shorter global BOLD-CSF coupling time-lags can predict an improved consciousness 6 months after enrollment, with an area under the receiver operating characteristic curve of 0.837, a sensitivity of 82.4%, and an accuracy of 85.7% using a cutoff point of 7.5.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The glymphatic system was impaired in patients with pDoC, and its function, measured by BOLD-CSF coupling, can serve as a novel prognostic biomarker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687952","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}