CNS Neuroscience & Therapeutics最新文献

{"title":"Anterior Cingulate Cortex Astrocytes Regulate Chronic Itch and Comorbid Negative Emotional Disorders in Mice.","authors":"Ze Fan, Xiaotong Shi, You Wu, Ningcan Ma, Ziyi Dai, Lisen Wang, Yushan Jin, Yuanyuan Zhu, Yiming Chen, Haopeng Zhang, Hui Zhang, Shengxi Wu, Jing Huang","doi":"10.1002/cns.71165","DOIUrl":"10.1002/cns.71165","url":null,"abstract":"<p><strong>Aims: </strong>The anterior cingulate cortex (ACC) is widely recognized as a key brain region in modulating itch and itch-associated behaviors. Though neuronal mechanisms are increasingly clarified, the role of ACC astrocytes remains poorly understood.</p><p><strong>Methods: </strong>By employing a diphenylcyclopropenone (DCP)-induced chronic itch mouse model, we assessed scratching behavior and negative emotions via behavioral tests. Astrocytic morphology was examined through immunofluorescence staining and sholl analysis. Fiber photometry was used to record calcium signals of ACC astrocytes and CaMKII-positive neurons. Chemogenetic manipulation was applied to modulate astrocyte activity. Gliotransmitter quantification was implemented to detect the gliotransmitter release in the ACC.</p><p><strong>Results: </strong>DCP induced robust scratching responses and concomitant anxiety- and depression-like behaviors. ACC astrocytes exhibited morphological activation and elevated calcium responses. Chemogenetic activation of ACC astrocytes alleviated DCP-induced scratching behavior and negative emotions, and enhanced calcium activity of local CaMKII-positive neurons. Conversely, chemogenetic inhibition of ACC astrocytes reduced such neuronal calcium activity. D-serine and ATP levels were reduced in DCP-induced chronic itch, while chemogenetic activation of astrocytes significantly elevated them.</p><p><strong>Conclusions: </strong>ACC astrocytes play a critical role in regulating chronic itch and comorbid anxiety-depression by modulating CaMKII-positive neuronal activity, providing a potential therapeutic target for intractable chronic itch in clinical settings.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71165"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987315","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":"Paeonol Alleviate Cisplatin- and Noise-Induced Hearing Loss by Preserving Hair Cell Ribosome Biogenesis.","authors":"Minhui Xia, Tianshi Sun, Wenyu Hou, Yiyun Lou, Yunjie Li, Hua Jiang, Hui Chai, Jiaoyao Ma, Mingyu Xia","doi":"10.1002/cns.71115","DOIUrl":"10.1002/cns.71115","url":null,"abstract":"<p><strong>Background: </strong>Hearing loss primarily results from irreversible cochlear hair cell (HC) damage caused by factors such as noise, aging, genetics, and ototoxic drugs including cisplatin. Currently, there are no effective clinical otoprotective agents available. The natural compound paeonol, derived from Paeonia suffruticosa, exhibits potential anti-inflammatory and antioxidant properties, positioning it as a promising therapeutic candidate given the central roles of oxidative stress and inflammation in hearing loss pathogenesis.</p><p><strong>Methods and results: </strong>Using mouse cochlear explant cultures, we demonstrated that paeonol protects against cisplatin-induced HC damage in a concentration-dependent manner and reduces the accumulation of MitoSOX, TNF-α, and IL-6. In vivo, paeonol administration not only prevented cisplatin-induced HC loss and inner HC synaptic degeneration but also conferred protection against noise-induced HC damage and hearing loss, demonstrating broad otoprotective efficacy. Mechanistically, RNA-seq analysis revealed that paeonol exerts its protective effect partly by preventing ribosome biogenesis dysfunction, thereby ensuring normal protein synthesis in HCs.</p><p><strong>Conclusions: </strong>Together, our work demonstrates the efficacy of paeonol across multiple models and reveals a potential protective mechanism, paving the way for its development as a much-needed otoprotective drug.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71115"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878737","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":"Impact of Preemptive vs. Conventional Tirofiban Administration on the Outcomes in Acute Branch Atheromatous Disease: A Propensity Score-Weighted Cohort Study.","authors":"Chunying Li, Ying Jin, Xing Liu, Ying Liu, Weikang Yang, Yue Wang, Dongsheng Ju","doi":"10.1002/cns.71120","DOIUrl":"10.1002/cns.71120","url":null,"abstract":"<p><strong>Background: </strong>Branch atheromatous disease (BAD) carries a high risk of early neurological deterioration (END). We evaluated the efficacy of preemptive tirofiban administration within 72 h compared with reactive rescue therapy following END.</p><p><strong>Methods: </strong>This retrospective, single-center study enrolled 221 patients with BAD-associated stroke. Based on the timing of tirofiban administration, patients were assigned to a preemptive intervention group (n = 127) or a conventional intervention group (n = 94). Preemptive intervention was defined as preemptive administration after clinical risk assessment, whereas conventional intervention was delayed until an increase of ≥ 2 points on the NIHSS score. Inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. Multivariable regression analysis was performed to identify independent predictors of an excellent 90-day outcome, defined as a modified Rankin Scale (mRS) score ≤ 1.</p><p><strong>Results: </strong>After IPTW adjustment, the preemptive intervention group showed a significantly higher rate of excellent 90-day outcomes (76.6% vs. 44.6%, p < 0.001) and a shorter median hospital stay (10 vs. 11 days, p = 0.02) compared with the conventional group. No between-group differences were observed in mortality or stroke recurrence (p > 0.05). Early tirofiban use (adjusted OR = 4.411, 95% CI: 2.349-8.283) and a lower baseline NIHSS score (adjusted OR = 0.832, 95% CI: 0.707-0.980) independently predicted favorable outcomes. Subgroup analyses confirmed consistent benefits across most strata, with patients aged over 65 years deriving greater neuroprotection (p = 0.004 for age-treatment interaction).</p><p><strong>Conclusion: </strong>Preemptive administration of tirofiban within the initial 72 h significantly improves 90-day neurological outcomes and reduces hospital stay length in patients with BAD-related stroke.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71120"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Multiple Inflammation-Derived Indices and the Risk of Post-Stroke Epilepsy.","authors":"Yu Wang, YeQin Gao, Long Wang","doi":"10.1002/cns.71143","DOIUrl":"10.1002/cns.71143","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke epilepsy (PSE) is a common and serious complication of stroke, yet simple and efficient risk assessment tools remain lacking in clinical practice. This study aimed to investigate the association between multiple core inflammation-derived indices and PSE, and to explore their potential reference value in risk stratification.</p><p><strong>Methods: </strong>In this retrospective case-control study, we extracted data from hospitalized stroke patients at Hefei Second People's Hospital between January 2018 and December 2025 from the electronic medical record system. A 1:1 propensity score matching method was used to balance confounding factors including sex, age, and underlying diseases. Ultimately, 317 PSE patients (case group) and 317 stroke patients without PSE (control group) were included. Routine hematological parameters collected within 24 h of admission were used to calculate six inflammatory indices: the systemic immune-inflammation index (SIRI), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-platelet ratio (NPR), and neutrophil-monocyte-to-lymphocyte ratio (NMLR). Multivariable logistic regression models were employed to analyze the association between inflammatory indices and PSE risk, and nonlinear relationships and threshold effects were also explored. The discriminative ability and incremental value of each inflammatory index were assessed using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Subgroup analyses were conducted to verify the stability of the results.</p><p><strong>Results: </strong>This study showed that for each one-standard-deviation increase in SIRI, the risk of PSE increased by 172% (OR = 2.72, FDR-adjusted p < 0.001). Quartile-stratified analysis revealed a clear dose-response relationship (trend p < 0.001). Similarly, the strength of association for SIRI was superior to that of other inflammation-derived indices. Compared with the other inflammatory indices, SIRI demonstrated relatively better discriminative ability in ROC analysis (AUC = 0.693, 95% CI: 0.654-0.732), NRI, and DCA. Restricted cubic spline regression and E-value analysis further supported the robustness of this association, and subgroup analyses indicated consistency across different subgroups.</p><p><strong>Conclusion: </strong>Systemic immune-inflammation index showed a relatively strong association with PSE risk and moderate discriminative ability in the stroke population, and may serve as an auxiliary reference indicator for early risk stratification of post-stroke epilepsy. However, its clinical utility requires further validation in prospective cohort studies.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71143"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904884","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":"Left Cerebellar-Right Frontal Uncoupling in Female First-Episode Major Depressive Disorder: Synaptic Evidence From [¹⁸F]UCB-H PET.","authors":"Juehan Wang, Yajun Lin, Tianfang Zhang, Pengfeng Xu, Shanyan Lei, Hong Yang, Zuobing Chen","doi":"10.1002/cns.71144","DOIUrl":"10.1002/cns.71144","url":null,"abstract":"<p><strong>Background: </strong>Synaptic loss is a neuropathological feature of depression.</p><p><strong>Objective: </strong>Cerebello-cerebral synaptic function was evaluated in female first-episode major depressive disorder (MDD) patients using [¹⁸F]UCB-H positron emission tomography (PET).</p><p><strong>Materials and methods: </strong>PET was performed on female first-episode MDD patients (FMD group, n = 7), healthy controls (HC group, n = 9), and chronic restraint stress (CRS) mice (n = 9). Standardized uptake value ratios (SUVR), voxel-wise tracer uptake analysis, functional connectivity (FC), and network analysis were performed at the cerebello-cerebral level. Associations with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) scores were assessed by Pearson correlation and logistic regression analysis.</p><p><strong>Results: </strong>In the FMD group, SUVR in the left cerebellum 7b was significantly reduced and negatively correlated with HAMD (r = -0.57) and HAMA (r = -0.55) scores. The cluster centered on the left cerebellar lobule VIII showed reduced tracer uptake and was negatively correlated with HAMD scores. FC was significantly reduced in the right frontal lobe but enhanced in the midbrain and occipital regions. The network was characterized by bilateral frontal lobe concentration in the FMD group, while the cerebellar network was more uniform. Cerebello-cerebral uncoupling between the left cerebellum and the right frontal lobe was observed, manifested as reduced SUVR correlation and weakened FC. CRS mice also showed reduced brain [¹⁸F]UCB-H uptake.</p><p><strong>Conclusions: </strong>Left cerebellar-right frontal uncoupling may serve as a potential neural correlate of first-episode MDD in females.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71144"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890594","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":"Exercise-Induced Myonectin Protects Against Cerebral Ischemia-Reperfusion Injury.","authors":"Jing Zhang, Shengle Chen, Jingyu Liu, Xin Qi, Xiaoming Zhang, Peng Lin, Dezhang Huang, Jing Li","doi":"10.1002/cns.71137","DOIUrl":"10.1002/cns.71137","url":null,"abstract":"<p><strong>Background: </strong>There exists muscle-brain signaling via myokines. However, not all members of myokines have been thoroughly studied. Here, we identify myonectin, an exercise-induced myokine, as a new regulator of cerebral ischemia-reperfusion (I/R) injury.</p><p><strong>Methods: </strong>Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO/R) in wild-type mice and skeletal muscle-specific myonectin-knockout mice. Laser speckle contrast imaging (LSCI) and TTC staining were used to assess cerebral injury. HT22 and BV2 cells were utilized to mimic I/R-associated cellular damage using oxygen-glucose deprivation and reoxygenation (OGD/R). Intravenous recombinant myonectin was administered to assess therapeutic effects on I/R injury. Immunohistochemistry, TUNEL, ELISA, and Western blotting assays were performed to detect morphological and molecular changes in cells and tissues.</p><p><strong>Results: </strong>Exercise elevated serum and brain myonectin and reduced infarct size and neuronal damage in wild-type but not myonectin-deficient mice after MCAO/R. Systemic myonectin administration significantly protected against cerebral I/R injury. Mechanically, myonectin exerted neuroprotective effects by suppressing excessive autophagic apoptosis and microglia-mediated neuroinflammation thorough activation of the PI3K/Akt/mTOR pathway.</p><p><strong>Conclusion: </strong>Skeletal muscle-derived myonectin protects the brain from I/R injury, contributing to exercise benefits via muscle-brain communication. Myonectin may serve as a promising therapeutic agent against cerebral I/R injury.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71137"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954521","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":"Neural Network Connection Characteristics Between Motor Cortex and Spinal Cord During Rat Bipedal Walking.","authors":"Pengcheng Xi, Xiaodan Lyu, Jiping He, Rongyu Tang, Yiran Lang","doi":"10.1002/cns.71160","DOIUrl":"10.1002/cns.71160","url":null,"abstract":"<p><strong>Object: </strong>Bipedal locomotion requires coordinated corticospinal interactions, yet how these networks dynamically reorganize across gait phases remains poorly understood. This study aimed to characterize the phase-dependent restructuring of corticospinal functional networks during rest, stance, and swing in healthy rats.</p><p><strong>Methods: </strong>Single-unit spiking activity was simultaneously recorded from the hindlimb motor cortex and lumbar spinal cord of healthy rats across three behavioral states: Rest, stance, and swing. Granger causality analysis was applied to local field potentials (LFPs) to assess directed functional connectivity. Total Spiking Probability Edges (TSPE) algorithm was used to estimate spike-train functional connectivity. Network topology was characterized by global efficiency and rich-club coefficient.</p><p><strong>Results: </strong>Granger causality revealed that corticospinal connectivity was most prominent in the beta band (13-35 Hz) during active locomotion. Global efficiency rose from rest (0.33) to stance (0.53) and swing (0.51). TSPE confirmed rich-club topology in all conditions. Spinal hub neurons predominated during locomotion, comprising 81.13% ± 15.5% of rich-club hubs at stance and 60.48% ± 10.21% at swing, while cortical and spinal hubs were balanced at rest. Mean latency decreased from 29.60 ± 20.66 ms at rest to 9.67 ± 1.65 ms during stance.</p><p><strong>Conclusions: </strong>The central nervous system dynamically restructures corticospinal functional networks across gait phases, with spinal hub neurons assuming a dominant role during active locomotion. This framework provides a mechanistic reference for studying corticospinal disruptions in spinal cord injury, Parkinson's disease, and stroke, and identifies phase-specific beta-band coupling and rich-club hub dynamics as candidate targets for closed-loop neural interfaces in gait rehabilitation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71160"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987324","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":"Limbic-Predominant Cortical Magnetic Susceptibility Alterations Are Associated With Glycemic Dysregulation and Cognitive Performance in Type 2 Diabetes.","authors":"Kun Wang, Dan Hu, Jiahe Wang, Ziyu Diao, Yuna Chen, Xuan Huang, Die Shen, Jie An, Shijun Qiu, Gang Li","doi":"10.1002/cns.71181","DOIUrl":"10.1002/cns.71181","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the spatial pattern of cortical magnetic susceptibility alterations in Type 2 diabetes mellitus (T2DM) and to determine whether hyperglycemia moderates the association between regional cortical QSM values and cognitive performance.</p><p><strong>Methods: </strong>In this cross-sectional study, 145 patients with T2DM and 182 healthy controls underwent 3 T MRI. Cortical gray matter magnetic susceptibility was quantified using quantitative susceptibility mapping (QSM). Cognitive function was assessed with a multidomain neuropsychological battery. Partial correlation, general linear models, and moderation analyses examined associations among cortical susceptibility, glycemic indices, and cognitive performance. Support vector regression (SVR) with nested cross-validation evaluated the predictive value of limbic subregional QSM values for information processing speed.</p><p><strong>Results: </strong>Whole-cortex analyses showed nominally higher QSM values in the bilateral limbic cortices of patients with T2DM, while post hoc analyses identified significantly higher QSM values in the left cingulate cortex and right parahippocampal gyrus after FDR correction. QSM values in selected limbic cortical regions at both the lobar and subregional levels were positively correlated with FPG and HbA1c. Covariate-adjusted analyses further indicated associations between higher QSM values in frontal, parietal, and limbic regions and poorer episodic memory and executive function. Moderation analyses suggested that higher HbA1c levels strengthened the inverse associations between QSM values in selected limbic cortical regions and cognitive performance on the MMSE, MoCA, and CDT. Within the T2DM group, SVR models based on limbic subregional QSM values showed cross-validated predictive performance for TMT-A scores.</p><p><strong>Conclusions: </strong>Patients with T2DM showed a limbic-predominant pattern of cortical magnetic susceptibility alterations, with higher QSM values in selected regions associated with poorer performance across multiple cognitive domains. HbA1c moderated the associations between regional QSM values and cognitive performance. These findings suggest that limbic cortical susceptibility alterations may be relevant to metabolic dysregulation and cognitive vulnerability in T2DM.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71181"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035929","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":"miR-15a-5p Regulates Ferroptosis in Glioblastoma by Targeting GLS2.","authors":"Yanyan Yu, Helan Yuan, Zikun Fang, Jinyuan Liao, Yancong Yang, Jun Liu, Wenjin Wei, Qiuhua Jiang","doi":"10.1002/cns.71097","DOIUrl":"10.1002/cns.71097","url":null,"abstract":"<p><strong>Aims: </strong>Glioblastoma (GBM) remains the most lethal primary brain tumor, and the molecular mechanisms driving its aggressiveness are incompletely understood. Recent multi-omics analyses have identified miR-15a-5p as one of the core microRNAs most closely associated with GBM. This study aimed to investigate the functional role and mechanism of miR-15a-5p in GBM pathogenesis.</p><p><strong>Methods: </strong>Expression of miR-15a-5p was analyzed in GBM tissues and cell lines. Genetic silencing experiments were performed to assess cell proliferation, migration, and tumor growth across multiple GBM cell lines and in an intracranial xenograft model. Ferroptosis-related changes were evaluated, and target validation was conducted using luciferase reporter assays. Rescue experiments were performed by co-modulating miR-15a-5p and GLS2.</p><p><strong>Results: </strong>miR-15a-5p was significantly overexpressed in GBM tissues and cell lines, and high expression correlated with poor patient survival. Genetic silencing of miR-15a-5p suppressed GBM cell proliferation and migration and inhibited tumor growth in vivo. Mechanistically, miR-15a-5p directly targeted the 3'UTR of glutaminase 2 (GLS2). Knockdown of miR-15a-5p induced ferroptosis-related features, including GPX4 downregulation, ACSL4 upregulation, iron accumulation, lipid peroxidation, and mitochondrial contraction. These effects were reversed by GLS2 knockdown in both in vitro and in vivo rescue experiments.</p><p><strong>Conclusion: </strong>The miR-15a-5p/GLS2 axis represents a previously unrecognized mechanism by which GBM cells resist ferroptosis. These findings not only define a novel mechanism underlying ferroptosis regulation in GBM but also identify the miR-15a-5p/GLS2 axis as a potential entry point for ferroptosis-based therapeutic intervention. Targeting this axis may provide a rational strategy to modulate ferroptosis and suppress GBM progression.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71097"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860467","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":"Correction to \"The Dual Associations of Peripheral Inflammatory Cells With Brain Reorganization in Insular Gliomas With/Without Epilepsy: An Exploratory Analysis\".","authors":"","doi":"10.1002/cns.71136","DOIUrl":"10.1002/cns.71136","url":null,"abstract":"","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71136"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885848","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}