CNS Neuroscience & Therapeutics最新文献

{"title":"Identification of a Novel Radiosensitivity-Related Signature and Validation of GPX8 in Regulating the Radiosensitivity of Glioma.","authors":"Gan Tao, Xiuli Guo, Fajian He, Sisi Yan, Qingwei Wang, Xiaowan Guo, Kehua Hu, Conghua Xie, Qiuji Wu, Yahua Zhong","doi":"10.1002/cns.70900","DOIUrl":"https://doi.org/10.1002/cns.70900","url":null,"abstract":"<p><strong>Background: </strong>Radioresistance is fundamental to glioma progression and poor prognosis. Understanding its underlying mechanisms and identifying novel therapeutic targets through elucidating key molecules in glioma radiosensitivity pathways are therefore of significant clinical importance.</p><p><strong>Methods: </strong>Radiosensitivity-related genes were identified based on radiotherapy response, glioma stemness, and prognosis. A predictive signature was constructed using Lasso-Cox regression and validated via clinicopathological, functional enrichment, immune infiltration, and correlation analyses. GPX8 expression and prognostic significance were assessed by tissue microarray. In vitro functional and radiobiological assays, complemented by in vivo subcutaneous xenograft models using BALB/c nude mice (treated with or without radiotherapy), evaluated the role of GPX8 in regulating malignant progression and radiosensitivity in glioma.</p><p><strong>Results: </strong>The radiosensitivity-related signature demonstrated significant potential in predicting glioma malignancy and prognosis, serving as an indicator of the mesenchymal subtype and contributing to the maintenance of an immunosuppressive microenvironment. GPX8 was overexpressed in high-grade gliomas and correlated with recurrence and poor survival. Knockdown of GPX8 suppressed the malignant biological behaviors of glioma cells. Radiation upregulated GPX8 expression while GPX8 knockdown significantly enhanced the cytotoxicity of radiation and induced apoptosis by promoting oxidative stress and DNA damage. Suppression of GPX8 effectively potentiated radiosensitivity in murine xenograft models and reduced intratumoral infiltration of tumor-associated macrophages.</p><p><strong>Conclusions: </strong>The radiosensitivity-related signature serves as a significant predictor for assessing glioma malignancy and prognosis. GPX8 acts as a key regulator of malignant phenotypes and radiosensitivity in glioma, positioning it as a promising therapeutic target to counteract both malignant progression and radioresistance.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70900"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758236","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":"Clinical Utility of Z-Score Distribution Mapping in Epileptogenic Zone Localizations.","authors":"Jinkun Han, Penghu Wei, Sichang Chen, Yanfeng Yang, Yongzhi Shan, Guoguang Zhao","doi":"10.1002/cns.70876","DOIUrl":"https://doi.org/10.1002/cns.70876","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the clinical utility of positron emission tomography (PET)-based Z-score distribution mapping (Z-map) in the noninvasive presurgical localization of seizure onset zones (SOZs), with a particular focus on regional differences in performance and methodological robustness.</p><p><strong>Methods: </strong>We analyzed a cohort of 120 patients with drug-resistant epilepsy who underwent stereoelectroencephalography (SEEG) implantation between 2021 and 2024. Multimodal imaging data, including PET and structural MRI, were processed using FreeSurfer and 3D Slicer to reconstruct electrodes, segment gray matter, and generate Z-maps. Hypometabolic regions were defined as the bottom 0.5% of Z-scores. The classification performance of the Z-map was validated against SEEG-defined SOZs.</p><p><strong>Results: </strong>The Z-map showed high classification performance in the frontal and parietal lobes (sensitivity: 0.74/0.72; κ: 0.68/0.65), but reduced effectiveness in the temporal and insular lobes (sensitivity: 0.41/0.65; κ: 0.44/0.47). The overall specificity (0.94) and negative predictive value (0.91) indicated strong exclusionary capability. Regional disparities were primarily attributed to anatomical complexity and technical limitations.</p><p><strong>Conclusion: </strong>Z-map offers clinically valuable support for localizing SOZs in the frontal and parietal cortex and optimizing SEEG implantation, particularly in patients with inconclusive noninvasive findings. However, its limited sensitivity in temporal and insular regions and high dependency on preprocessing quality underscore the need for standardized pipelines and multimodal integration. Future research should focus on improving robustness and reproducibility to facilitate clinical translation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70876"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758238","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":"Whole-Brain Neural Connectivity to Cholinergic Neurons in the Lower Thoracic Intermediolateral Column.","authors":"Yuan-Jun Yang, Kai-Ying Zhang, Bin-Bin Li, Xia-Wan Liu, Jing-Rong Li, Yi-Nuo Liu, Yu-Han Liu, Ji Li, Xiang-Shan Yuan, Ming Zhong","doi":"10.1002/cns.70902","DOIUrl":"https://doi.org/10.1002/cns.70902","url":null,"abstract":"<p><strong>Objective: </strong>The intermediolateral column (IML) serves as a crucial hub for sympathetic information processing between the brain and peripheral organs, with its defining hallmark being the presence of cholinergic neurons expressing choline acetyltransferase (ChAT). Specifically, the IML of the lower thoracic cord plays a pivotal role in regulating abdominal metabolic and digestive viscera. However, little is known about the whole-brain neural connectivity targeting these lower thoracic IML cholinergic neurons, necessitating further investigation.</p><p><strong>Methods: </strong>Specific retrograde tracing virus was injected into the lower thoracic IML of ChAT-Cre transgenic mice expressing Cre in the cholinergic neurons. After the virus has fully expressed, brain and spinal cord sections were prepared for whole-brain fluorescence imaging and quantitative analysis.</p><p><strong>Results: </strong>We found that virally labeled neurons were detected in 40 brain regions of ChAT-Cre mice, encompassing the telencephalon, diencephalon, and brainstem. Afferents were predominantly concentrated in 25 brainstem regions, with the pons providing the highest total number of afferents and the medulla offering the highest afferent density across both hemispheres. Although a small subset of regions exhibited strictly unilateral inputs or hemispheric preference, the overall projection pattern remained bilateral. Furthermore, our results revealed extensive projections to the IML from regions classically implicated in sympathetic outflow regulation and homeostatic control, including the paraventricular hypothalamic nucleus (PVN), lateral hypothalamic area (LH), and rostroventrolateral reticular nucleus (RVLM). In addition, inputs were also observed from motor-related regions, such as primary and secondary motor cortices (M1, M2), red nucleus (RN), and gigantocellular reticular nucleus (Gi), suggesting a potential anatomical basis for the central coupling of somatic motor and sympathetic functions.</p><p><strong>Conclusion: </strong>Our study provides a comprehensive whole-brain anatomical map of inputs to lower thoracic IML cholinergic neurons. This extensive supraspinal network, integrating classical sympathetic and homeostatic centers with motor-related regions, suggests a potential anatomical basis for the central coordination of somatic motor and autonomic functions.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70902"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758257","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":"Treatment Response and Prognosis of Primary Angiitis of the Central Nervous System: A Real-World Observation.","authors":"Xin Liu, Ti Wu, Linlin Yin, Fu-Dong Shi, Huabing Wang","doi":"10.1002/cns.70884","DOIUrl":"10.1002/cns.70884","url":null,"abstract":"<p><strong>Subject: </strong>To analyze the treatment response in patients with primary angiitis of the central nervous system (PACNS) in a large vasculitis cohort.</p><p><strong>Method: </strong>In this single-center retrospective observational study, we assessed treatment, relapses, remission, and outcome of patients with PACNS. We pooled the patients' relapses under different treatments as well as various immunotherapies. Multivariate logistic regression analysis was performed to determine factors independently associated with relapse and those associated with good functional status. The time of observation was 96 months.</p><p><strong>Result: </strong>The cohort comprised 80 patients, with 38 diagnosed with pathologically confirmed PACNS and 42 with clinically diagnosed PACNS, with a median follow-up duration of 18 months (range 3-96). Treatment comprised acute-phase induction therapy with high-dose corticosteroids, alone or combined with immunosuppressive agents, followed by remission-phase maintenance immunosuppressive therapy, primarily with cyclophosphamide, rituximab, or mycophenolate mofetil. Following treatment, 49 patients (61.3%) achieved remission and 70 (87.5%) attained favorable functional outcomes. The overall relapse rate was 35%. Group 3 demonstrated significantly higher baseline disease severity (p < 0.05). Multivariate analysis identified seizures and cognitive impairment as predictors of relapse.</p><p><strong>Conclusion: </strong>This study demonstrates that a majority of PACNS patients exhibit a favorable response to therapy. For patients presenting with more severe disease at diagnosis, long-term maintenance therapy following remission induction with glucocorticoids or immunosuppressive agents is required.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70884"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696876","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":"Evolution of Drug Development Trends in Multiple Sclerosis: Analysis of Mainland China and Global Landscapes From 2004 to 2024.","authors":"Chaoyang Chen, Zhenyu Niu, Ting Yang, Xuanling Zhang, Ran Wei, Xiaocong Pang, Ran Liu, Ying Zhou","doi":"10.1002/cns.70870","DOIUrl":"10.1002/cns.70870","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a leading cause of nontraumatic disability in young adults. Over the past two decades, pharmacotherapy for MS has advanced substantially. This study analyzes global trends in MS clinical trial activity, regional distribution, and drug development pipelines and compares research and development (R&D) patterns between mainland China and global settings to provide insights into future MS drug development.</p><p><strong>Methods: </strong>MS-related clinical trials registered between November 1, 2004, and October 31, 2024, were retrieved from ClinicalTrials.gov, the EU Clinical Trials Register (EUCTR), the Center for Drug Evaluation (CDE) of China, and the Chinese Clinical Trial Registry (ChiCTR). Trial characteristics, including phase, sponsorship, geography, drug class, and therapeutic targets, were systematically analyzed and compared between mainland China and the global datasets.</p><p><strong>Results: </strong>A total of 1183 MS clinical trials were identified, including 83 conducted in mainland China. Overall, 967 trials (81.74%) were interventional and 216 (18.26%) were observational. Industry-sponsored trials accounted for 67.06% of all studies. Globally, MS clinical trial activity increased rapidly during the first decade and showed a more moderate pace after 2015, whereas trial numbers in mainland China rose sharply after 2018. This recent expansion in China was largely driven by bioequivalence (BE) studies and late-phase trials. After normalizing by the number of prevalent MS cases, substantial geographic heterogeneity in clinical trial density persisted. Europe consistently exhibited high case-adjusted trial density, while mainland China remained in the lower-to-middle categories. Chemical drugs accounted for a slightly higher number of registered trials than biologics. The most frequently investigated therapeutic targets across all trials were IFNAR, CD20, and S1PR1. A subset of studies also explored dual-target strategies.</p><p><strong>Conclusions: </strong>This registry-based study provides a comprehensive overview of global and mainland China MS drug clinical trials from 2004 to 2024. While global trial activity remained sustained over the past two decades, trial registrations in mainland China increased markedly in recent years, although the development structure differed from global patterns, with a higher proportion of BE studies and late-phase trials. These findings provide a reference for MS clinical drug development.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70870"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643467","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":"ADAMTS-7 Increase Contributes to Worsened Neurological Outcome in Mice on High Fat Diet.","authors":"Yang Xu, Jun Li, Zhiyi Zuo","doi":"10.1002/cns.70877","DOIUrl":"10.1002/cns.70877","url":null,"abstract":"<p><strong>Background: </strong>Obesity and associated metabolic disturbance are associated with worse outcomes after brain ischemia. Cerebrovascular remodeling mediated by matrix metalloproteinase 9 (MMP-9) may contribute to this poor outcome. A disintegrin and metalloproteinase-7 (ADAMTS-7) has been shown to regulate vascular remodeling in peripheral vessels. This study was designed to determine the role of ADAMTS-7 in regulating MMP-9 activity, cerebrovascular remodeling and neurological outcomes in mice.</p><p><strong>Methods: </strong>Six-week-old CD-1 male mice were fed regular diet (RD) or high fat diet (HFD) for 10 weeks before they had left middle cerebral arterial occlusion (MCAO) for 1.5 h. Their brains were harvested for Western blotting, immunostaining or cerebral vascular casting. Lentiviral particles containing shRNA targeting ADAMTS-7 mRNA or scramble shRNA were injected intracerebroventricularly.</p><p><strong>Results: </strong>HFD feeding increased ADAMTS-7 and MMP-9 activity, reduced middle cerebral arterial root diameter, and worsened neurological outcomes after the MCAO. Silencing ADAMTS-7 attenuated these HFD-induced effects. ADAMTS-7 was expressed in the neurons, astrocytes, oligodendrocytes, and blood vessels in the brain.</p><p><strong>Conclusions: </strong>HFD increased ADAMTS-7 to lead to MMP-9 activation, which then induces cerebrovascular remodeling and poor neurological outcomes after brain ischemia. ADAMTS-7 is expressed in multiple cell types in the brain.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70877"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669290","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":"ANGPT2/Tie2 Enhances H3K18la-Mediated Macrophage M2 Polarization to Promote Endothelial Cell Proliferation in the Chronically Ischaemic Brain.","authors":"Chuyang Tai, Cong Ling, Yang Yang, Ni Mo, Cian Yao, Songtian Lv, Baoyu Zhang, Hui Wang, Chuan Chen","doi":"10.1002/cns.70879","DOIUrl":"10.1002/cns.70879","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate the specific mechanism by which angiopoietin-2 (ANGPT2)/Tie2 signaling in macrophages promotes endothelial cell (EC) proliferation in the chronically ischaemic brain (CIB).</p><p><strong>Methods: </strong>We first analyzed the polarization status of primary Tie2-expressing macrophages (TEMs) and Tie2-overexpressing THP-1-derived macrophages (Tie2-TDMs) following ANGPT2 treatment and detected the expression of representative proangiogenic factors. Subsequently, lysine lactylation (Kla) levels were measured, and chromatin immunoprecipitation (ChIP) assays were performed to explore the downstream activity of ANGPT2/Tie2 signaling. Additionally, in vitro functional assays using human umbilical vein endothelial cells (HUVECs) and in vivo experiments in a rat model of chronic cerebral ischaemia were conducted to confirm the effect of ANGPT2/Tie2-regulated macrophages on angiogenesis.</p><p><strong>Results: </strong>In response to ANGPT2 treatment, the expression of M2 polarization markers and proangiogenic factors increased in TEMs and Tie2-TDMs. Concurrently, LDHA and H3K18la were elevated, and ChIP assays confirmed the regulatory role of ANGPT2/Tie2 signaling in H3K18la-mediated transcriptional regulation. The viability of HUVECs cocultured with Tie2-TDMs was increased. Finally, ANGPT2 overexpression increased M2-polarized TEM infiltration in the CIB; additionally, rats injected with ANGPT2-pretreated TEMs exhibited more prominent EC proliferation.</p><p><strong>Conclusion: </strong>ANGPT2/Tie2 induces the H3K18la-mediated M2 polarization of macrophages to facilitate EC proliferation and angiogenesis in the CIB.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70879"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669308","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 of the Triglyceride-Glucose (TyG) Index and TyG-BMI With 1-Year Outcomes Following Endovascular Treatment in Acute Basilar Artery Occlusion.","authors":"Qiuting Wang, Haodong Li, Yuxin Chen, Na Liu, Lu Yang, Chuanjie Wu, Wenbo Zhao, Longfei Wu, Liqun Jiao, Sijie Li, Qingfeng Ma, Xunming Ji, Chuanhui Li","doi":"10.1002/cns.70898","DOIUrl":"https://doi.org/10.1002/cns.70898","url":null,"abstract":"<p><strong>Background: </strong>Long-term outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (BAO) vary substantially, yet metabolic correlates remain incompletely characterized. This study evaluated whether the triglyceride-glucose (TyG) index and TyG-body mass index (TyG-BMI) are associated with 1-year functional status and mortality after EVT.</p><p><strong>Methods: </strong>A single-center registry with prospective data collection was retrospectively analyzed. Consecutive acute BAO patients undergoing EVT within 24 h (December 2012-September 2024) were included. Unfavorable functional outcome at 1 year was defined as modified Rankin Scale (mRS) 4-6; 1-year all-cause mortality was also assessed. Multivariable logistic regression was applied, with receiver operating characteristic analyses and prespecified subgroup analyses.</p><p><strong>Results: </strong>The final cohort comprised 298 patients (median age 62 years; 78.5% male), among whom 165 (55.4%) had an unfavorable 1-year outcome and 109 (36.6%) died. After adjustment, each 1-SD increase in TyG and TyG-BMI corresponded to higher odds of unfavorable outcome (TyG OR 1.69, 95% CI 1.25-2.30; TyG-BMI OR 1.46, 95% CI 1.10-1.96) as well as mortality (TyG OR 1.44, 95% CI 1.09-1.90; TyG-BMI OR 1.61, 95% CI 1.23-2.12). Discrimination was modest and similar between indices. A significant sex interaction was observed for TyG-BMI and mortality (p for interaction = 0.03), with an association in men only.</p><p><strong>Conclusions: </strong>In EVT-treated acute BAO, TyG and TyG-BMI may help identify EVT-treated acute BAO patients at higher risk of poor 1-year outcome and death. The mortality risk associated with TyG-BMI was modified by sex, with an effect confined to men.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70898"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758148","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":"Depression Mediates the Association Between Ambient Air Pollution and Gastrointestinal/Liver Diseases: A Prospective Cohort Study.","authors":"Yanqi Kou, Shicai Ye, Mouji Liang, Lei Ge, Ling Qin, Yanping Ha, Yuan Tian, Botao Luo, Chunyi Wu, Liping Zhan, Ke Yang, Zhuoyan Lu, Yuping Yang","doi":"10.1002/cns.70878","DOIUrl":"10.1002/cns.70878","url":null,"abstract":"<p><strong>Background: </strong>The escalating burden of gastrointestinal (GI) and liver diseases poses a critical public health challenge, with emerging evidence implicating air pollution as a modifiable risk factor. However, the mechanistic pathways, particularly the mediating role of depression in the pollution-disease nexus, remain underexplored. This study investigates the longitudinal associations between ambient air pollution exposure and GI/liver diseases in a nationwide cohort, with a focus on quantifying depression's mediating effects.</p><p><strong>Methods: </strong>Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020; n = 18,755), we evaluated the impact of long-term exposure to PM₁, PM_2.5, PM₁₀, SO₂, CO, NO₂, and O₃ on incident GI/liver diseases. Multivariable-adjusted Cox proportional hazards models incorporated demographic, socioeconomic (region, education, retirement status), and lifestyle (smoking, drinking) covariates. Mediation analysis assessed the proportion of total effects mediated by depression (CESD-10 scores).</p><p><strong>Results: </strong>Chronic exposure to PM₁ (HR = 1.33, 95% CI: 1.30-1.37), PM_2.5 (HR = 1.30, 1.26-1.33), PM₁₀ (HR = 1.29, 1.25-1.32), SO₂ (HR = 1.64, 1.60-1.69), CO (HR = 1.47, 1.43-1.51), and NO₂ (HR = 1.27, 1.23-1.30) per interquartile range increase was significantly associated with elevated disease risk, whereas O₃ exhibited protective effects (HR = 0.77, 0.74-0.79). Depression mediated 4.0%-11.3% of pollution effects, with the highest mediation observed for O₃ (11.3%) and lowest for SO₂ (4.0%). Stratified analyses revealed heightened vulnerability in rural residents, individuals with lower education, and Northeastern populations.</p><p><strong>Conclusions: </strong>This study pioneers the identification of depression as a mediator linking air pollution to GI/liver diseases in a nationally representative cohort. The findings advocate for integrative policies targeting air quality improvement and mental health interventions to alleviate the dual burden of environmental and psychological morbidity.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70878"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696866","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":"Pathological Roles of Astrocytes in Traumatic Brain Injury.","authors":"Di Wu, Yuxiao Ma, Baofeng Wang, Yongtao Zheng, Jie Ren, Qingfang Sun, Liuguan Bian, Yuhao Sun","doi":"10.1002/cns.70856","DOIUrl":"10.1002/cns.70856","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes participate in both neuropathological and protective processes following traumatic brain injury (TBI) and undergo various characteristic changes, including phenotypic transformation, transcriptional reprogramming, and functional diversification.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted in PubMed using key terms \"astrocytes\" and \"traumatic brain injury\", and we integrated this existing evidence from transcriptomic analyses to mechanistic studies to elucidate the role and underlying mechanisms of astrocytes in TBI pathophysiology.</p><p><strong>Results: </strong>Transcriptomic analyses reveal distinct astrocyte phenotypes: neurotoxic A1 astrocytes and neuroprotective A2 astrocytes. Beyond this binary framework, single-cell studies have identified intermediate astrocyte states, underscoring the need for more nuanced functional profiling. TBI triggers astrocyte activation via classic signaling pathways in response to mechanical stress, damage-associated molecular patterns (DAMPs), and cytokines. These pathways-TLR4/NF-κB, JAK/STAT3, and MAPK-form an interactive signaling network, enabling astrocytes to integrate diverse injury signals into coordinated responses that drive subsequent pathological effects. Dysregulation of astrocytic ion channels and transporters disrupts ionic homeostasis, exacerbating cytotoxic and vasogenic edema. Mitochondrial dysfunction and reactive oxygen species overproduction further amplify neuronal damage through lipid peroxidation and excitotoxicity. Interactions between astrocytes and microglia, macrophages, and endothelial cells promote neuroinflammation, blood-brain barrier disruption, synaptic and axonal dysfunction, and neuronal apoptosis via mediators such as matrix metalloproteinases, vascular endothelial growth factor, and adhesion molecules. Additionally, reactive astrocytes inhibit neural regeneration through glial scar formation and secretion of inhibitory molecules.</p><p><strong>Conclusions: </strong>By combining mechanistic studies with translational perspectives, this review highlights that astrocytes act as central mediators of secondary injury and repair in TBI pathology. Given the context-dependent nature of astrocyte signaling, future therapeutic strategies should aim to reprogram astrocyte responses with temporal and cell-type precision rather than pursuing broad inhibition. Also, targeting astrocyte-specific pathways, such as the TLR4 and NF-κB pathways, may mitigate secondary injury and improve outcomes. This underscores the therapeutic potential of modulating astrocyte responses in the treatment of TBI.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70856"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669269","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}