To assess whether early plasma inflammatory proteins identify SVD-related stroke patients at high risk of cognitive impairment and to examine imaging-mediated effects.
Methods
This single-center retrospective study (April 2020–August 2024) enrolled patients with MRI-confirmed recent small subcortical infarct (RSSI) and healthy controls. GFAP and NLRP3 levels were measured by ELISA. MRI markers of small vessel disease—including white matter hyperintensities (WMH), lacunes, perivascular spaces, and microbleeds—were evaluated. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and functional outcome by the modified Rankin Scale (mRS) at 3 months. Associations were analyzed using correlation, regression, and mediation analyses.
Results
A total of 108 RSSI patients and 47 controls were included (mean age 57.9 ± 10.5 years; 64.1% male). RSSI patients had significantly higher plasma GFAP and NLRP3 levels (p < 0.05). Both proteins were inversely associated with total MoCA scores and cognitive subdomains, but not with 3-month mRS. GFAP and NLRP3 correlated positively with periventricular WMH (PWMH). Mediation analysis showed that PWMH accounted for 23.88%–28.10% of the association between plasma protein levels and cognitive impairment.
Conclusions
Elevated plasma GFAP and NLRP3 are associated with post-stroke cognitive impairment in RSSI, partially mediated by PWMH. These biomarkers may help identify patients at risk of early cognitive decline.
{"title":"Plasma GFAP and NLRP3 Associate with Cognitive Impairment After Recent Small Subcortical Infarct via Periventricular White Matter Hyperintensity","authors":"Tianxiang Lan, Chunhua Wang, Yuying Yan, Tang Yang, Jingyu Cui, Rumei Lei, Rongfeng Luo, Shuai Jiang, Bo Wu","doi":"10.1002/cns.70780","DOIUrl":"10.1002/cns.70780","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess whether early plasma inflammatory proteins identify SVD-related stroke patients at high risk of cognitive impairment and to examine imaging-mediated effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-center retrospective study (April 2020–August 2024) enrolled patients with MRI-confirmed recent small subcortical infarct (RSSI) and healthy controls. GFAP and NLRP3 levels were measured by ELISA. MRI markers of small vessel disease—including white matter hyperintensities (WMH), lacunes, perivascular spaces, and microbleeds—were evaluated. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and functional outcome by the modified Rankin Scale (mRS) at 3 months. Associations were analyzed using correlation, regression, and mediation analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 108 RSSI patients and 47 controls were included (mean age 57.9 ± 10.5 years; 64.1% male). RSSI patients had significantly higher plasma GFAP and NLRP3 levels (<i>p</i> < 0.05). Both proteins were inversely associated with total MoCA scores and cognitive subdomains, but not with 3-month mRS. GFAP and NLRP3 correlated positively with periventricular WMH (PWMH). Mediation analysis showed that PWMH accounted for 23.88%–28.10% of the association between plasma protein levels and cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated plasma GFAP and NLRP3 are associated with post-stroke cognitive impairment in RSSI, partially mediated by PWMH. These biomarkers may help identify patients at risk of early cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211708","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}
This study aimed to explore the relationship between sleep duration and intracranial atherosclerosis and cerebral small vessel disease (CSVD), and pinpoint the potential mediating factors.
Methods
Data were derived from the cross-sectional baseline survey of the PRECISE (Poly-vascular Evaluation for Cognitive Impairment and Vascular Events) study. Participants were divided into short sleep (< 7 h), normal sleep (7–9 h), and long sleep (> 9 h) groups. The associations of sleep duration with intracranial atherosclerotic plaque, intracranial atherosclerotic burden, total CSVD score, and CSVD imaging markers were evaluated.
Results
We enrolled 3038 participants (53.5% women; mean age: 61.2 ± 6.7 years). A long sleep duration was correlated with a higher risk of intracranial atherosclerotic plaque (long vs. normal: odds ratio [OR], 1.40 [95% CI, 1.10–1.78]), intracranial atherosclerotic burden (long vs. normal: common OR, 1.38 [95% CI, 1.09–1.75]), enlarged perivascular space in the basal ganglia (BG-EPVS) (long vs. normal: OR, 1.45 [95% CI, 1.07–1.97]); a short sleep duration indicated a rise in lacune (short vs. normal: OR, 1.67 [95% CI, 1.06–2.63]) after adjustment for covariates. The association of a long sleep duration with intracranial atherosclerotic plaque, intracranial atherosclerotic burden, and BG-EPVS (mediation percentage: 35.4%, 34.0%, 20.3%, respectively) was partially mediated by metabolic factors of blood pressure and fasting plasma glucose.
Conclusion
Aberrant sleep duration may increase the potential risk for intracranial atherosclerosis and CSVD, which can be partially mediated by blood pressure and fasting plasma glucose. These findings highlight the benefits of clinical management of metabolic factors for those with aberrant sleep duration to prevent intracranial atherosclerosis and CSVD.
{"title":"Association of Sleep Duration With Intracranial Atherosclerosis and Cerebral Small Vessel Disease: A Mediation by Metabolic Factors","authors":"Hongbin Chen, Anqi Zhang, Weiqi Chen, Xueli Cai, Mengyuan Zhou, Shan Li, Jing Jing, Tiemin Wei, Yongjun Wang, Yuesong Pan, Yilong Wang","doi":"10.1002/cns.70797","DOIUrl":"10.1002/cns.70797","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to explore the relationship between sleep duration and intracranial atherosclerosis and cerebral small vessel disease (CSVD), and pinpoint the potential mediating factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were derived from the cross-sectional baseline survey of the PRECISE (Poly-vascular Evaluation for Cognitive Impairment and Vascular Events) study. Participants were divided into short sleep (< 7 h), normal sleep (7–9 h), and long sleep (> 9 h) groups. The associations of sleep duration with intracranial atherosclerotic plaque, intracranial atherosclerotic burden, total CSVD score, and CSVD imaging markers were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We enrolled 3038 participants (53.5% women; mean age: 61.2 ± 6.7 years). A long sleep duration was correlated with a higher risk of intracranial atherosclerotic plaque (long vs. normal: odds ratio [OR], 1.40 [95% CI, 1.10–1.78]), intracranial atherosclerotic burden (long vs. normal: common OR, 1.38 [95% CI, 1.09–1.75]), enlarged perivascular space in the basal ganglia (BG-EPVS) (long vs. normal: OR, 1.45 [95% CI, 1.07–1.97]); a short sleep duration indicated a rise in lacune (short vs. normal: OR, 1.67 [95% CI, 1.06–2.63]) after adjustment for covariates. The association of a long sleep duration with intracranial atherosclerotic plaque, intracranial atherosclerotic burden, and BG-EPVS (mediation percentage: 35.4%, 34.0%, 20.3%, respectively) was partially mediated by metabolic factors of blood pressure and fasting plasma glucose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Aberrant sleep duration may increase the potential risk for intracranial atherosclerosis and CSVD, which can be partially mediated by blood pressure and fasting plasma glucose. These findings highlight the benefits of clinical management of metabolic factors for those with aberrant sleep duration to prevent intracranial atherosclerosis and CSVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>NCT03178448</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211642","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}
Xiaolong Xi, Zhensen Chen, Chaojun Wang, Fei Wang, Xuedong Sun
Background
After spinal cord injury (SCI), neuronal lipid peroxidation and excessive production of reactive oxygen species (ROS) induced by secondary injury exacerbate ferroptosis, impeding regenerative repair and functional recovery in mice. Thus, clarifying the molecular and cellular mechanisms underlying the inhibition of neuronal ferroptosis post-SCI is crucial.
Methods
Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) were used to analyze changes in the transcription factor CREB5 post-SCI. Combined with in vitro (primary neuron experiments) and in vivo (mouse SCI model) studies, CREB5 was knocked down/overexpressed, and ApoL6 was overexpressed. Indicators related to neuronal ferroptosis (ROS, lipid peroxidation, free fatty acids, etc.) and functional recovery in mice were detected.
Results
After SCI, the transcriptional activity of the transcription factor CREB5 is enhanced, and its expression level first increases and then decreases. Mechanistically, CREB5 inhibits the decomposition of neuronal lipid droplets (LDs) by enhancing the transcriptional activity of the lipolysis-related protein ApoL6, reducing the release of free fatty acids (FFA) and fatty acid oxidation (FAO), thereby decreasing ROS generation and lipid peroxidation, and ultimately inhibiting neuronal ferroptosis. In vitro experiments showed that CREB5 knockdown exacerbates neuronal death and inhibits axonal growth; in vivo experiments demonstrated that CREB5 knockdown hinders axonal growth and functional recovery in mice post-SCI, while ApoL6 overexpression partially reverses these impairments.
Conclusions
CREB5 maintains the balance of neuronal lipid droplet metabolism by regulating ApoL6 and serves as a potential therapeutic target for inhibiting neuronal ferroptosis after SCI.
{"title":"CREB5 Inhibits Neuronal Ferroptosis via Transactivating ApoL6 to Regulate Lipid Droplet Metabolism After Spinal Cord Injury","authors":"Xiaolong Xi, Zhensen Chen, Chaojun Wang, Fei Wang, Xuedong Sun","doi":"10.1002/cns.70783","DOIUrl":"10.1002/cns.70783","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>After spinal cord injury (SCI), neuronal lipid peroxidation and excessive production of reactive oxygen species (ROS) induced by secondary injury exacerbate ferroptosis, impeding regenerative repair and functional recovery in mice. Thus, clarifying the molecular and cellular mechanisms underlying the inhibition of neuronal ferroptosis post-SCI is crucial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) were used to analyze changes in the transcription factor CREB5 post-SCI. Combined with in vitro (primary neuron experiments) and in vivo (mouse SCI model) studies, CREB5 was knocked down/overexpressed, and ApoL6 was overexpressed. Indicators related to neuronal ferroptosis (ROS, lipid peroxidation, free fatty acids, etc.) and functional recovery in mice were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After SCI, the transcriptional activity of the transcription factor CREB5 is enhanced, and its expression level first increases and then decreases. Mechanistically, CREB5 inhibits the decomposition of neuronal lipid droplets (LDs) by enhancing the transcriptional activity of the lipolysis-related protein ApoL6, reducing the release of free fatty acids (FFA) and fatty acid oxidation (FAO), thereby decreasing ROS generation and lipid peroxidation, and ultimately inhibiting neuronal ferroptosis. In vitro experiments showed that CREB5 knockdown exacerbates neuronal death and inhibits axonal growth; in vivo experiments demonstrated that CREB5 knockdown hinders axonal growth and functional recovery in mice post-SCI, while ApoL6 overexpression partially reverses these impairments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CREB5 maintains the balance of neuronal lipid droplet metabolism by regulating ApoL6 and serves as a potential therapeutic target for inhibiting neuronal ferroptosis after SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211663","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}
Adnan Akif, Mohammad Fahim Kadir, Md. Rabiul Islam
Background
Major Depressive Disorder (MDD) is a leading cause of disability, and limitations of the monoamine hypothesis have driven the exploration of complementary models, including the inflammatory hypothesis. This hypothesis suggests that in a subset of patients, immune dysregulation, especially involving interleukins (ILs), contributes to depression. This review compares IL dysregulation in MDD and autoimmune diseases to identify common and unique inflammatory mechanisms for treatment.
Results and Conclusion
Some MDD patients exhibit chronic, low-grade inflammation both systemically (in blood) and centrally (in CSF and brain). They show elevated pro-inflammatory IL-6, IL-1β, and IL-18, with insufficient anti-inflammatory IL-10. This immune dysregulation affects key neurobiological processes (monoamine metabolism, HPA axis, neurogenesis), linking inflammation to depressive symptoms. MDD and autoimmune diseases share inflammatory mediators and signaling pathways, supporting these as therapeutic targets; however, MDD's inflammation is low-grade and innate driven, whereas autoimmune diseases have high-grade, adaptive immune responses to specific antigens. Successful anti-IL therapies in autoimmune conditions provide a roadmap for treating inflammation-driven depression. Translating these findings to practice requires a precision immune-psychiatry approach. Biomarkers like C-reactive protein and IL-6 can identify an inflammatory depression subtype, and patients may benefit from targeted immunomodulatory strategies, repurposed biologics, novel small molecules, or lifestyle interventions particularly if standard antidepressants fail.
{"title":"Interleukins in Major Depressive Disorder: Lessons From Autoimmune Diseases and Pathways to Clinical Translation","authors":"Adnan Akif, Mohammad Fahim Kadir, Md. Rabiul Islam","doi":"10.1002/cns.70791","DOIUrl":"10.1002/cns.70791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Major Depressive Disorder (MDD) is a leading cause of disability, and limitations of the monoamine hypothesis have driven the exploration of complementary models, including the inflammatory hypothesis. This hypothesis suggests that in a subset of patients, immune dysregulation, especially involving interleukins (ILs), contributes to depression. This review compares IL dysregulation in MDD and autoimmune diseases to identify common and unique inflammatory mechanisms for treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>Some MDD patients exhibit chronic, low-grade inflammation both systemically (in blood) and centrally (in CSF and brain). They show elevated pro-inflammatory IL-6, IL-1β, and IL-18, with insufficient anti-inflammatory IL-10. This immune dysregulation affects key neurobiological processes (monoamine metabolism, HPA axis, neurogenesis), linking inflammation to depressive symptoms. MDD and autoimmune diseases share inflammatory mediators and signaling pathways, supporting these as therapeutic targets; however, MDD's inflammation is low-grade and innate driven, whereas autoimmune diseases have high-grade, adaptive immune responses to specific antigens. Successful anti-IL therapies in autoimmune conditions provide a roadmap for treating inflammation-driven depression. Translating these findings to practice requires a precision immune-psychiatry approach. Biomarkers like C-reactive protein and IL-6 can identify an inflammatory depression subtype, and patients may benefit from targeted immunomodulatory strategies, repurposed biologics, novel small molecules, or lifestyle interventions particularly if standard antidepressants fail.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206098","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}
Licorice (Glycyrrhiza spp.), a traditional Chinese herb, contains glycyrrhetinic acid derivatives with neuroprotective properties but limited bioavailability.
Purpose
YCY-20 is a novel derivative synthesized by structural modification of 18β-glycyrrhetinic acid. The aim of this study is to explore its therapeutic effect and potential molecular mechanism on cerebral ischemia–reperfusion injury (CIRI).
Methods
Pharmacokinetic profiling was performed to compare plasma exposure and brain distribution of YCY-20 and its parent compound 18β-GA. Neuroprotection was assessed using middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cells. Evaluations included infarct volume (TTC staining), apoptosis (TUNEL, flow cytometry), and protein dynamics (Western blot). Network pharmacology identified potential targets, and in vivo experiments are conducted to validate the relevant molecular pathways.
Results
YCY-20 exhibited improved pharmacokinetic properties, with higher and more stable plasma concentrations and detectable brain levels after oral administration, compared with 18β-GA. YCY-20 administration significantly attenuated body weight loss, cerebral infarct volume, and neuronal apoptosis in MCAO/R rats. Mechanistically, YCY-20 suppressed the MCAO/R-induced upregulation of pro-apoptotic proteins (Bax, caspase-3, cleaved caspase-3) while restoring anti-apoptotic Bcl-2 expression. In vitro OGD/R models corroborated these anti-apoptotic effects. Network analysis identified AGE-RAGE/MAPK signaling as the predominant pathway modulated by YCY-20, with subsequent in vivo validation demonstrating its capacity to downregulate key mediators in this pathway.
Conclusions
YCY-20 confers protection against CIRI, at least partially through apoptosis inhibition mediated by AGE-RAGE/MAPK signaling pathway modulation. This study provides preclinical evidence for developing licorice-derived agents in stroke management.
{"title":"Novel Glycyrrhizinic Acid Derivative YCY-20 Inhibits Cerebral Ischemia/Reperfusion Induced Apoptosis via the AGE-RAGE/MAPK Pathway","authors":"Jia Luo, Xue Qin, Jiaxin Chen, Xiushi Yu, Ziyun Liu, Jiyi Lv, Xinhui Pan, Yong Chen, Lili Wei","doi":"10.1002/cns.70792","DOIUrl":"10.1002/cns.70792","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Licorice (<i>Glycyrrhiza</i> spp.), a traditional Chinese herb, contains glycyrrhetinic acid derivatives with neuroprotective properties but limited bioavailability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>YCY-20 is a novel derivative synthesized by structural modification of 18<i>β</i>-glycyrrhetinic acid. The aim of this study is to explore its therapeutic effect and potential molecular mechanism on cerebral ischemia–reperfusion injury (CIRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pharmacokinetic profiling was performed to compare plasma exposure and brain distribution of YCY-20 and its parent compound 18<i>β</i>-GA. Neuroprotection was assessed using middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cells. Evaluations included infarct volume (TTC staining), apoptosis (TUNEL, flow cytometry), and protein dynamics (Western blot). Network pharmacology identified potential targets, and in vivo experiments are conducted to validate the relevant molecular pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>YCY-20 exhibited improved pharmacokinetic properties, with higher and more stable plasma concentrations and detectable brain levels after oral administration, compared with 18<i>β</i>-GA. YCY-20 administration significantly attenuated body weight loss, cerebral infarct volume, and neuronal apoptosis in MCAO/R rats. Mechanistically, YCY-20 suppressed the MCAO/R-induced upregulation of pro-apoptotic proteins (Bax, caspase-3, cleaved caspase-3) while restoring anti-apoptotic Bcl-2 expression. In vitro OGD/R models corroborated these anti-apoptotic effects. Network analysis identified AGE-RAGE/MAPK signaling as the predominant pathway modulated by YCY-20, with subsequent in vivo validation demonstrating its capacity to downregulate key mediators in this pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>YCY-20 confers protection against CIRI, at least partially through apoptosis inhibition mediated by AGE-RAGE/MAPK signaling pathway modulation. This study provides preclinical evidence for developing licorice-derived agents in stroke management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.70792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211697","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}
<div> <section> <h3> Background</h3> <p>Sleep problems have emerged as a critical health concern in the digital age, yet the complex mechanisms linking technology use to sleep disruption remain poorly understood. Previous research has typically examined isolated relationships between specific technological behaviors and sleep outcomes, overlooking the complex interplay among various digital factors. This study aims to address this gap by employing network analysis to investigate the interconnected relationships among multiple technology-related factors and their collective influence on sleep problems.</p> </section> <section> <h3> Methods</h3> <p>Using network analysis, this study examined how different aspects of digital technology use collectively influence sleep problems in a large sample of Chinese adults (<i>N</i> = 9443). Participants were recruited through stratified random sampling based on age groups and geographical regions, with the sample size determined a priori using Monte Carlo simulations to ensure stable network estimation. Participants completed validated measures assessing screen time, before-bed electronic device use, electronic device dependency, social media anxiety, digital information overload, virtual social pressure, blue light exposure, circadian rhythm disruption, online gaming addiction, work-life digital integration, and sleep problems. Participants with diagnosed sleep disorders, those engaged in shift work, or those who had traveled across time zones in the past month were excluded to minimize confounding effects on natural sleep patterns.</p> </section> <section> <h3> Results</h3> <p>Network analysis revealed complex interconnections among technology-related factors and sleep problems. Blue light exposure demonstrated the strongest direct edge weight with sleep problems (<i>r</i> = 0.31, <i>p</i> < 0.001), followed by circadian rhythm disturbance (<i>r</i> = 0.26, <i>p</i> < 0.001). The network structure indicated that screen time, bedtime device use, electronic device dependence, virtual social pressure, and work-life digital integration showed weaker direct associations with sleep problems but demonstrated substantial indirect pathways through intermediate variables. Online gaming addiction, digital information overload, social media anxiety, and circadian rhythm disturbance exhibited moderate centrality indices, suggesting their role as potential mediators within the network.</p> </section> <section> <h3> Conclusions</h3> <p>These findings advance our understanding of technology-induced sleep disruption and
{"title":"Digital Sleep Disruption: Unraveling the Network Structure of Technology Use and Sleep Problems Through Network Analysis","authors":"Haoqing Gan, Lingjia Xu, Chenglin Tong","doi":"10.1002/cns.70778","DOIUrl":"10.1002/cns.70778","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sleep problems have emerged as a critical health concern in the digital age, yet the complex mechanisms linking technology use to sleep disruption remain poorly understood. Previous research has typically examined isolated relationships between specific technological behaviors and sleep outcomes, overlooking the complex interplay among various digital factors. This study aims to address this gap by employing network analysis to investigate the interconnected relationships among multiple technology-related factors and their collective influence on sleep problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using network analysis, this study examined how different aspects of digital technology use collectively influence sleep problems in a large sample of Chinese adults (<i>N</i> = 9443). Participants were recruited through stratified random sampling based on age groups and geographical regions, with the sample size determined a priori using Monte Carlo simulations to ensure stable network estimation. Participants completed validated measures assessing screen time, before-bed electronic device use, electronic device dependency, social media anxiety, digital information overload, virtual social pressure, blue light exposure, circadian rhythm disruption, online gaming addiction, work-life digital integration, and sleep problems. Participants with diagnosed sleep disorders, those engaged in shift work, or those who had traveled across time zones in the past month were excluded to minimize confounding effects on natural sleep patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network analysis revealed complex interconnections among technology-related factors and sleep problems. Blue light exposure demonstrated the strongest direct edge weight with sleep problems (<i>r</i> = 0.31, <i>p</i> < 0.001), followed by circadian rhythm disturbance (<i>r</i> = 0.26, <i>p</i> < 0.001). The network structure indicated that screen time, bedtime device use, electronic device dependence, virtual social pressure, and work-life digital integration showed weaker direct associations with sleep problems but demonstrated substantial indirect pathways through intermediate variables. Online gaming addiction, digital information overload, social media anxiety, and circadian rhythm disturbance exhibited moderate centrality indices, suggesting their role as potential mediators within the network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings advance our understanding of technology-induced sleep disruption and","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199515","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}
Emerging evidence indicates that ferroptosis characterized by lipid peroxidation is becoming a promising therapeutic strategy in glioma. However, the role of the MBOAT family, key regulators of membrane phospholipids remodeling in ferroptosis, remains unexplored in glioma.
Methods
We systematically analyzed the expression and clinical significance of MBOAT1 in glioma using TCGA, CGGA, GEO, and GTEx databases. Functional mechanisms were investigated through enrichment, single-cell RNA sequencing, and immune infiltration analyses. We experimentally validated the oncogenic role of MBOAT1 in GBM through both in vivo and in vitro experiments.
Results
MBOAT1 expression was elevated in glioma and correlated with increased grades and poor patient prognosis. Cox regression analysis identified MBOAT1 as an independent prognostic factor. Functional enrichment analysis and single cell RNA-seq analysis revealed that MBOAT1 is associated with enhanced ferroptosis resistance. Furthermore, the immune infiltration analysis and cell communication analysis suggested that MBOAT1 promotes an immunosuppressive microenvironment. Experiments confirmed that overexpression of MBOAT1 promoted GBM cell proliferation, migration, invasion, and ferroptosis resistance, while its knockdown had the opposite effect.
Conclusion
Our findings suggest that MBOAT1 promotes glioma progression by mediating ferroptosis resistance and is related to an immunosuppressive microenvironment, highlighting its potential as an independent prognostic biomarker and a promising therapeutic target.
{"title":"MBOAT1 Promotes Glioma Progression Through Enhancing Ferroptosis Resistance and Immunosuppressive Microenvironment","authors":"Junqi Fan, Qingqing Huang, Lanxin Bao, Xueran Chen, Zhiyou Fang, Haifeng Shu","doi":"10.1002/cns.70785","DOIUrl":"10.1002/cns.70785","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emerging evidence indicates that ferroptosis characterized by lipid peroxidation is becoming a promising therapeutic strategy in glioma. However, the role of the MBOAT family, key regulators of membrane phospholipids remodeling in ferroptosis, remains unexplored in glioma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We systematically analyzed the expression and clinical significance of MBOAT1 in glioma using TCGA, CGGA, GEO, and GTEx databases. Functional mechanisms were investigated through enrichment, single-cell RNA sequencing, and immune infiltration analyses. We experimentally validated the oncogenic role of MBOAT1 in GBM through both in vivo and in vitro experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MBOAT1 expression was elevated in glioma and correlated with increased grades and poor patient prognosis. Cox regression analysis identified MBOAT1 as an independent prognostic factor. Functional enrichment analysis and single cell RNA-seq analysis revealed that MBOAT1 is associated with enhanced ferroptosis resistance. Furthermore, the immune infiltration analysis and cell communication analysis suggested that MBOAT1 promotes an immunosuppressive microenvironment. Experiments confirmed that overexpression of MBOAT1 promoted GBM cell proliferation, migration, invasion, and ferroptosis resistance, while its knockdown had the opposite effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that MBOAT1 promotes glioma progression by mediating ferroptosis resistance and is related to an immunosuppressive microenvironment, highlighting its potential as an independent prognostic biomarker and a promising therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199589","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}
T. Chu, C. Sun, Y. Zheng, et al. “Study on the Mechanisms of Ischemic Stroke Impacting Sleep Homeostasis and Circadian Rhythms in Rats.” CNS Neuroscience & Therapeutics 31, no. 2 (2025): e70153. https://doi.org/10.1111/cns.70153.
The author identified a duplication error in Figure 7A, where the Western blot bands for Per1(2d-6h) and Cry1(2d-6h) were mistakenly replicated during image compilation. We wish to emphasize that the original experimental data remain intact and verifiable. This error does not impact the quantitative analysis, results, or conclusions of the study. The corrected Figure 7A is provided below.
{"title":"Correction to “Study on the Mechanisms of Ischemic Stroke Impacting Sleep Homeostasis and Circadian Rhythms in Rats”","authors":"","doi":"10.1002/cns.70776","DOIUrl":"10.1002/cns.70776","url":null,"abstract":"<p>T. Chu, C. Sun, Y. Zheng, et al. “Study on the Mechanisms of Ischemic Stroke Impacting Sleep Homeostasis and Circadian Rhythms in Rats.” <i>CNS Neuroscience & Therapeutics</i> 31, no. 2 (2025): e70153. https://doi.org/10.1111/cns.70153.</p><p>The author identified a duplication error in Figure 7A, where the Western blot bands for Per1(2d-6h) and Cry1(2d-6h) were mistakenly replicated during image compilation. We wish to emphasize that the original experimental data remain intact and verifiable. This error does not impact the quantitative analysis, results, or conclusions of the study. The corrected Figure 7A is provided below.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12902884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177049","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}
Tissue plasminogen activator (tPA)–induced cerebral hemorrhagic transformation (HT) after ischemic stroke limits its clinical use widely. Pachymic acid, a main active component of Poria cocos, mitigates brain ischemia/reperfusion injury, but its effect on tPA-induced HT is unclear.
Methods
A focal middle cerebral artery occlusion/reperfusion model was established and administered with tPA and pachymic acid. Infarct volume and neurological function were assessed at 24 h after reperfusion. Blood–brain barrier (BBB) damage was evaluated using Evans blue leakage, immunofluorescence, and Western blot. Pachymic acid and PI3K protein interaction was identified using molecular docking, molecular dynamics (MD) simulation, and surface plasmon resonance (SPR).
Results
Compared with the tPA group, pachymic acid dose-dependently improves neurological and motor functions, reduces infarct volume and hemorrhagic volume, and alleviates permeability and tight junction protein degradation of BBB after ischemic stroke, with the strongest effects observed at the highest dose. Molecular docking, MD simulation, and SPR results indicate that pachymic acid can directly bind to PI3K protein. Further experiments showed that the PI3K inhibitor LY294002 reversed pachymic acid's protective effects.
Conclusions
This study demonstrated that pachymic acid protects the BBB by targeting PI3K to activate the PI3K/Akt signaling pathway, thereby alleviating tPA-induced HT after ischemic stroke.
{"title":"Pachymic Acid Targets PI3K/Akt Signaling Pathway to Attenuate tPA-Induced Hemorrhagic Transformation After Ischemic Stroke","authors":"Yongshi Wu, Tong Zhang, Ruoqi Li, Yige Wu, Congmin Wei, Fangming Sun, Shanshan Zhang, Xiang Fan","doi":"10.1002/cns.70782","DOIUrl":"10.1002/cns.70782","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tissue plasminogen activator (tPA)–induced cerebral hemorrhagic transformation (HT) after ischemic stroke limits its clinical use widely. Pachymic acid, a main active component of <i>Poria cocos</i>, mitigates brain ischemia/reperfusion injury, but its effect on tPA-induced HT is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A focal middle cerebral artery occlusion/reperfusion model was established and administered with tPA and pachymic acid. Infarct volume and neurological function were assessed at 24 h after reperfusion. Blood–brain barrier (BBB) damage was evaluated using Evans blue leakage, immunofluorescence, and Western blot. Pachymic acid and PI3K protein interaction was identified using molecular docking, molecular dynamics (MD) simulation, and surface plasmon resonance (SPR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with the tPA group, pachymic acid dose-dependently improves neurological and motor functions, reduces infarct volume and hemorrhagic volume, and alleviates permeability and tight junction protein degradation of BBB after ischemic stroke, with the strongest effects observed at the highest dose. Molecular docking, MD simulation, and SPR results indicate that pachymic acid can directly bind to PI3K protein. Further experiments showed that the PI3K inhibitor LY294002 reversed pachymic acid's protective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrated that pachymic acid protects the BBB by targeting PI3K to activate the PI3K/Akt signaling pathway, thereby alleviating tPA-induced HT after ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193745","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}
Jing Zhou, Benjamin H. Wang, Jiangning Yu, Guoxiang Wang, Jingyi Cai, Mohan Yu, Kehua Chen, Li Wan, Xu Liu, Zhigang Yang, Yulong Wang, Yun Wang
Background
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined.
Methods
Using a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen–glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment.
Results
MCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (EGABA), diminished GABAergic inhibition, and increased neuronal excitability. Preventing KCC2 downregulation with FUR or CLP290 suppressed epileptiform activity in vitro and increased seizure thresholds in vivo. Ischemia induced robust microglial activation and increased BDNF release. Pharmacological inhibition of microglia (minocycline) or TrkB (K252a) effectively restored KCC2 expression, normalized EGABA, and reduced post-stroke seizure severity.
Conclusion
Our findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy.
{"title":"KCC2 Dysfunction Mediated by Microglial BDNF/TrkB Signaling Exacerbates Early Post-Stroke Seizure Susceptibility","authors":"Jing Zhou, Benjamin H. Wang, Jiangning Yu, Guoxiang Wang, Jingyi Cai, Mohan Yu, Kehua Chen, Li Wan, Xu Liu, Zhigang Yang, Yulong Wang, Yun Wang","doi":"10.1002/cns.70795","DOIUrl":"10.1002/cns.70795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen–glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (<i>E</i><sub><i>GABA</i></sub>), diminished GABAergic inhibition, and increased neuronal excitability. Preventing KCC2 downregulation with FUR or CLP290 suppressed epileptiform activity in vitro and increased seizure thresholds in vivo. Ischemia induced robust microglial activation and increased BDNF release. Pharmacological inhibition of microglia (minocycline) or TrkB (K252a) effectively restored KCC2 expression, normalized <i>E</i><sub><i>GABA</i></sub>, and reduced post-stroke seizure severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193788","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}
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