CNS Neuroscience & Therapeutics最新文献

{"title":"The Dual Role of Gastrodin in Spinal Cord Injury: Microglial Phenotype Switching and Neuronal Survival via PI3K/AKT Activation","authors":"Jingsheng Feng,&nbsp;Shutao Gao,&nbsp;Yukun Hu,&nbsp;Weibin Sheng","doi":"10.1002/cns.70811","DOIUrl":"10.1002/cns.70811","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) triggers a complex secondary cascade, the defining feature of which is neuroinflammation. This amplifies tissue damage and impedes neurological recovery. Microglial polarization is a critical event in this process, yet effective modulation strategies remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate whether gastrodin (GAS), a natural phenolic glycoside, could provide neuroprotection and promote functional recovery following SCI by modulating microglial polarization and to elucidate the underlying molecular mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a combination of behavioral, histological, and molecular assays, and a microglia–neuron co-culture system under inflammatory conditions, using a rat contusion SCI model and LPS-stimulated BV2 microglia in vitro. The role of the PI3K/AKT signaling pathway was specifically investigated using the inhibitor LY294002.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The administration of GAS markedly enhanced locomotor function, diminished lesion volume, and promoted neuronal survival in a dose-dependent manner in vivo. GAS mitigated the inflammatory response by reducing M1 markers (iNOS and CD86) and augmenting M2 markers (Arg1 and CD206) within the injured spinal cord and BV2 microglia. Additionally, GAS exhibited a direct anti-apoptotic effect on neurons in co-culture. Mechanistically, GAS significantly activated the PI3K/AKT signaling pathway. Notably, the PI3K inhibitor LY294002 completely nullified the anti-inflammatory and anti-apoptotic effects of GAS, underscoring the central role of this pathway in mediating GAS's effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that GAS confers multifaceted protection against SCI by modulating microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and by directly inhibiting neuronal apoptosis, primarily through activation of the PI3K/AKT signaling pathway. These findings indicate that GAS holds significant potential as a therapeutic candidate for the treatment of SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615453","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":"Perivascular SPP1 Drives Microglial Synaptic Engulfment After Ischemic Stroke.","authors":"Chenchen Xu, Xiaoxiao Li, Nan Cheng, Rui Zhao, Xin Wang, Wenxin Xia, Jianjian Dong, Yongsheng Han","doi":"10.1002/cns.70886","DOIUrl":"https://doi.org/10.1002/cns.70886","url":null,"abstract":"<p><strong>Objective: </strong>Following ischemic stroke (IS), activated microglia activity could contribute to neuronal injury and blood-brain barrier (BBB) disruption. The upstream vascular-derived signal initiating this transition remains unclear; therefore, we investigated whether perivascular SPP1 regulates microglia-mediated synapse engulfment during IS.</p><p><strong>Methods: </strong>Male C57BL/6 mice were assigned to sham, shSpp1, middle cerebral artery occlusion/reperfusion (MCAO/R), and MCAO/R + shSpp1 groups. Cerebral perfusion was assessed using laser speckle contrast imaging and super-resolution vascular imaging, while neuronal injury was evaluated using Nissl and TUNEL staining. Proteomic profiling of the ischemic penumbra identified regulators of microglia-mediated synaptic remodeling. Synaptic structure and glial-vascular unit (GVU) integrity were examined using transmission electron microscopy, immunofluorescence, and molecular analyses. Behavioral outcomes were assessed using the open-field, Barnes maze, rotarod, and wire-hanging tests.</p><p><strong>Results: </strong>Compared with sham controls, MCAO/R mice displayed increased microglial synaptic engulfment and ultrastructural synaptic damage in the ischemic penumbra, accompanied by reduced synaptic protein expression. Proteomic analysis revealed upregulation of inflammatory and vascular-related pathways, with marked upregulation of SPP derived from perivascular macrophages. Spp1 silencing attenuated neuroinflammation, reduced infarct volume, improved cerebral perfusion, preserved GVU integrity, and alleviated behavioral deficits. Spp1 suppression also reduced microglial synaptic engulfment in vivo and restored synaptic protein and mRNA levels in vitro.</p><p><strong>Conclusion: </strong>Targeting perivascular SPP1 suppresses excessive microglia-mediated synaptic engulfment, preserves BBB integrity and synaptic architecture, and offers a GVU-centered therapeutic strategy for IS.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70886"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758241","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":"Development of a Novel Prognostic Inflammation Index to Predict Poor Outcomes in Patients With Intracerebral Hemorrhage: A Longitudinal Study.","authors":"Guangyong Chen, Feng Chen, Xin Lu, Zhangjing Zhu, Fangyan Chen, Qian Liu, Ziming Ren, Changhao Zhang, Yuxin Zhu, Yueping Chen, Suwen Huang, Dehao Yang, Yiyun Weng","doi":"10.1002/cns.70904","DOIUrl":"https://doi.org/10.1002/cns.70904","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous intracerebral hemorrhage (ICH) is an acute cerebrovascular disease associated with high mortality and severe disability. Inflammation plays a critical role in the onset and progression of ICH. However, existing inflammatory markers have limited predictive capacity for the prognosis of ICH patients. This study aims to develop a novel Prognostic inflammation index (PII) based on leukocyte subset counts and evaluate its effectiveness in assessing the prognosis of ICH patients.</p><p><strong>Methods: </strong>A total of 1021 consecutive ICH patients hospitalized between January 2021 and June 2023 were included as the derivation cohort. In addition, an internal temporal validation cohort of 366 patients hospitalized between January 2024 and December 2024 was assembled using identical inclusion/exclusion criteria. Using reduced-rank regression (RRR) based on leukocyte subsets (including neutrophils, monocytes, lymphocytes, eosinophils, and basophils), we constructed the PII. Multivariate logistic regression was employed to analyze the associations between PII, its dynamic trajectories, and patient outcomes, including poor prognosis, all-cause mortality, and stroke-associated infections. The predictive performance of PII was illustrated using a nomogram, and its efficacy was compared to conventional inflammatory markers through receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>Patients with elevated PII were significantly associated with poor outcomes at 3, 6, and 12 months, stroke-associated infections, and all-cause mortality within 1 year (all p < 0.05). PII trajectory analysis revealed that patients with persistently high PII had a substantially increased risk of poor outcomes (p < 0.05). Moreover, compared to common systemic inflammatory markers such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI), PII showed generally favorable discriminative performance across most endpoints; however, the pairwise AUC comparisons were exploratory and some comparisons yielded borderline p values that should be interpreted cautiously.</p><p><strong>Conclusion: </strong>PII, a composite inflammation index based on leukocyte subset counts, is an effective predictor of poor outcomes in ICH patients and shows favorable prognostic performance compared with traditional inflammatory markers.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70904"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758252","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":"An Optimized Conversion of Spermatogonial Stem Cells Into Spinal Cord Neurons Enhances Functional Recovery in Rats After Spinal Cord Injury.","authors":"Xinyu Guo, Yongjie Zhang, Haihong Zhang, Hao Yang","doi":"10.1002/cns.70844","DOIUrl":"10.1002/cns.70844","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The inflammatory response following spinal cord injury (SCI) is a critical factor contributing to neural dysfunction. This response exacerbates neural damage in the injured area by facilitating the infiltration of inflammatory cells and the release of cytokines, thereby remarkably impeding neural repair and functional recovery. Spermatogonial stem cells (SSCs) have the potential for spinal cord nerve regeneration. Concurrently, olfactory ensheathing cells (OECs), a unique cell type with neurorepair potential, can effectively enhance nerve regeneration through the secretion of various neurotrophic factors, the suppression of inflammatory responses, and improvements in the injury microenvironment. However, research concerning OEC induction systems and the differentiation of SSCs into spinal cord neurons remains limited. This study aimed to investigate the synergistic effects of OECs and SSCs to develop a more effective and safe stem cell therapy strategy for SCI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study integrates in vitro and in vivo methodologies to investigate the mechanisms through which an efficient induction system facilitates the differentiation of SSCs into neurons. Initially, primary SSCs were cultured and characterized through immunofluorescence, and the molecular mechanisms underlying the induction system were examined via western blot and quantitative reverse transcription (qRT-PCR) methods. An inflammatory environment was subsequently developed in a lipopolysaccharide (LPS)-activated microglial model to evaluate the impact of the induction system on SSC differentiation. Finally, differentiated SSCs were transplanted into a traumatic SCI model, and functional recovery was assessed via the Basso, Beattie and Bresnahan (BBB) locomotor scale, as well as electrophysiology, including somatosensory evoked potential (SEP) and motor evoked potential (MEP) tests.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vitro experimental results demonstrated that the activation of the OEC induction system significantly enhanced the efficiency of the differentiation of SSCs into spinal cord neurons. Notably, in the inflammatory milieu, an optimal concentration of lipopolysaccharide (LPS) significantly augments both neuronal differentiation efficiency and survival rates. In addition, compared with those in the other experimental groups, the induced neuronal-like cells exhibited genuine neuronal characteristics. Importantly, JAK2/STAT3 pathway signaling plays a crucial role in this intricate cellular transformation. Suppression of the JAK2/STAT3 signaling pathway significantly improved differentiation efficiency and facilitated neural repair. In vivo experimental results revealed that the transplantation of differentiated spinal neurons into the lesioned spinal cord substantially improved sensory and motor functions, as evidenced by behavioral assessments (such as BBB scoring) and electrophysiological tests (MEP and SEP).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70844"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687231","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":"Genetic Association of Sexual Behavior, Sildenafil, and Hormonal Contraceptives With Mental Disorders.","authors":"Zhongliang Lin, Kejing Zhu, Renke He, Xueying Liu, Qinyu Luo, Haiyan Wu, Zhaoying Jiang, Jiaen Yu, Jianzhong Sheng, Hong Zhu, Hefeng Huang","doi":"10.1002/cns.70861","DOIUrl":"10.1002/cns.70861","url":null,"abstract":"<p><strong>Background: </strong>The observational research indicates that risky sexual activities contribute to the development of mental disorders. However, the potential causal effects of sexual behaviors, sildenafil use, and hormonal contraceptive use on mental disorders remain unclear.</p><p><strong>Methods: </strong>We applied two-sample Mendelian randomization (univariable and multivariable MR) to assess the effects of age at first sex (AFS) and number of sexual partners (NSP) on mental disorders and sex differences, using Genome-Wide Association Studies (GWAS) data from UK Biobank and FinnGen. An observational analysis using NHANES 2015-2016 was conducted for validation. We further used expression quantitative trait loci (eQTL) to proxy drug target genes and examined the impact of sildenafil and contraceptives on mental disorders using SMR and IVW-MR methods.</p><p><strong>Results: </strong>We found that an increased genetically predicted AFS was associated with decreasing anxiety disorders, bipolar affective disorders, depression, disturbance of activity and attention (DAA), and post-traumatic stress disorder. An increased genetically predicted NSP was associated with increasing anxiety disorders, bipolar affective disorders, depression, and post-traumatic stress disorder. SMR analysis found that PDE11A, instead of PDE5A, a drug target for sildenafil, causes DAA. Suggestive evidence was observed regarding the positive association between progesterone receptor expression and risk of depression. Notably, given the exploratory nature of the multiple analyses, these findings require replication in independent cohorts to confirm causal relationships.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70861"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696921","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":"Fulminant Adrenal Crisis as the Initial Healthcare System Presentation of Adolescent Cerebral X-Linked Adrenoleukodystrophy.","authors":"Junqiu Zhou, Wei Meng, Wei Zhao, Chenguang Shen","doi":"10.1002/cns.70914","DOIUrl":"https://doi.org/10.1002/cns.70914","url":null,"abstract":"","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70914"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758164","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":"Glycemic Status and Effect of Immediate Intensive Statin on Mild Ischemic Stroke: A Subgroup Analysis of the INSPIRES Trial.","authors":"Lingling Jiang, Zihao Deng, Ying Gao, Xuan Wang, Yingying Yang, Tingting Wang, Yuesong Pan, Weiqi Chen, Yilong Wang","doi":"10.1002/cns.70882","DOIUrl":"https://doi.org/10.1002/cns.70882","url":null,"abstract":"<p><strong>Aims: </strong>A subgroup analysis of the Intensive Statin and Antiplatelet Therapy for High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial to evaluate intensive statin effects in patients with ischemic stroke by glycemic status.</p><p><strong>Method: </strong>Patients were stratified into three subgroups based on glycemic status: without type 2 diabetes mellitus (T2DM), with newly diagnosed T2DM, with a history of T2DM. The primary outcomes included stroke and moderate-to-severe bleeding, whereas secondary outcomes comprised composite vascular events, poor functional outcomes, and any bleeding within 90 days.</p><p><strong>Results: </strong>Among 6100 patients, 4038 were without T2DM, 404 had a newly diagnosed T2DM, and 1658 had a history of T2DM. No significant risk reduction of stroke was observed with immediate versus delayed statin therapies across glycemic subgroups (p for interaction = 0.29). Compared to delayed-intensive statin, immediate-intensive statin treatment was associated with reduced risk of poor functional outcome in non-T2DM patients (adjusted relative risk 0.71, 95% CI 0.57-0.90; p = 0.004), but no benefit in those with newly diagnosed T2DM or those with a history of T2DM (p for interaction = 0.003). There was no glycemic status by treatment interaction for risk of bleeding or composite vascular event.</p><p><strong>Conclusions: </strong>Patients without T2DM derived greater benefit in functional outcomes from immediate-intensive statin after ischemic stroke than those with T2DM.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70882"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanism Underlying the Abnormal Expression of α-Synuclein in the Cortical Lesions of Patients With FCD Type IIb and TSC.","authors":"Li Zhang, Jian-Ping Song, Jun Huang, Ping Liang, Hui Yang, Chun-Qing Zhang, Kai-Feng Shen","doi":"10.1002/cns.70893","DOIUrl":"https://doi.org/10.1002/cns.70893","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to investigate the underlying mechanisms of abnormal expression of α-synuclein (α-syn) in cortical lesions of focal cortical dysplasia IIb (FCD IIb) and tuberous sclerosis complex (TSC).</p><p><strong>Methods: </strong>Cortical lesions of patients with FCD IIb and TSC were obtained during the surgery, FCD rats were generated by in utero X-ray radiation. Immunostaining, RT-PCR, Western blotting, and electroencephalography recording were conducted in this study. α-syn was intraventricularly injected; mTOR inhibitor (rapamycin) and glutamate transporter-1 (GLT-1) enhancer (ceftriaxone sodium) were intraperitoneally injected before the following experiments.</p><p><strong>Results: </strong>mTOR and p-mTOR expressed in the dysmorphic neurons, vimentin-positive balloon cells, and giant cells, whereas the mTOR/p-mTOR ratio was decreased in FCD IIb and TSC lesions. α-syn was decreased, while p-α-syn was increased in the cortex of FCD animals, whereas they were rescued by inhibition of mTOR with rapamycin. The expression of GLT-1 was decreased and modulated by rapamycin in FCD animals. Enhancement of the function of GLT-1 with ceftriaxone ameliorated α-synucleinopathy and seizure activities in FCD animals. Additionally, intracerebroventricular injection of α-syn exerted anti-seizure effects.</p><p><strong>Conclusions: </strong>Our results showed that modulation of the mTOR/GLT-1 pathway ameliorated α-synucleinopathy and seizure activities in FCD, providing insights for understanding the epileptogenic mechanisms of FCD IIb and TSC.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70893"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758275","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":"Cystatin B Attenuates Cerebral Ischemia Reperfusion Injury by Inhibiting the JAK2/STAT3 Signaling Pathway.","authors":"Gang Zhou, Fengjiao Hu, Ju Gao, Lei Wang, Xiangbo Wu, Yu Tian, Peng Zhang, Guangming Xia, Feng Wan, Jinhua Wang","doi":"10.1002/cns.70818","DOIUrl":"10.1002/cns.70818","url":null,"abstract":"<p><strong>Background: </strong>Cerebral ischemia reperfusion injury (CIRI) poses a significant clinical and economic burden worldwide. Therefore, it is essential to identify key regulators that may improve stroke prognosis. Cystatin B (CSTB) is known to be involved in neuroprotection, inflammation modulation, and apoptosis regulation, but its specific function and mechanisms in CIRI remain unclear.</p><p><strong>Methods: </strong>We employed gain- and loss-of-function approaches in a mouse model of transient middle cerebral artery occlusion (t/MCAO) and in cultured neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R). The effects were evaluated primarily using a combination of quantitative PCR, Western blot, and immunofluorescence staining to assess neurological deficits, inflammatory responses, and apoptosis, as well as to elucidate the underlying mechanisms.</p><p><strong>Results: </strong>Our findings demonstrated that CSTB significantly attenuated CIRI, as evidenced by the mitigation of neurological deficits, inflammation, and apoptosis. Mechanistically, the protective effects of CSTB were associated with the suppression of the JAK2/STAT3 signaling pathway.</p><p><strong>Conclusion: </strong>This study identifies CSTB as a novel negative regulator of CIRI. Its protective role is mediated through the inhibition of apoptosis and inflammatory responses via the JAK2/STAT3 axis, suggesting its potential as a therapeutic target for ischemic stroke.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70818"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571551","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":"CircRbfox1 Contributes to Colonic Hypersensitivity in Rats With Diabetes by Altering HuC Subcellular Localization to Regulate RBFOX1 Expression.","authors":"Shiyu Zhang, Ji Hu, Chendong Ni, Yilian Zhang, Jiahao Chen, Yajing Liu, Shufen Hu, Fuchao Zhang, Guang-Yin Xu, Hong-Hong Zhang","doi":"10.1002/cns.70896","DOIUrl":"https://doi.org/10.1002/cns.70896","url":null,"abstract":"<p><strong>Aims: </strong>The purpose of this study was to explore the molecular mechanism of circRNA mediated colonic hypersensitivity in rats with diabetes.</p><p><strong>Methods: </strong>Intraperitoneal injection of streptozocin female rats was used to induce Type 1 Diabetes Mellitus. A combination of molecular biology and behavioral approaches was used to investigate the role of circRbfox1 in the pathogenesis of colonic hypersensitivity in diabetic rats.</p><p><strong>Results: </strong>A new circular RNA-Rbfox1, derived from the host gene encoding RNA-Binding Protein Fox1, as a mechanism of visceral pain is identified. We confirmed that circRbfox1 remarkably upregulated in T13-L2 dorsal root ganglions in rats with diabetes, and could interact with the RNA-binding protein HuC to promote its transition from the cytosol into the nucleus to promote the translation level of RBFOX1. In addition, the increased expression of Rbfox1 could further promote colonic hypersensitivity in diabetic rats by regulating the expression of Cav1.3.</p><p><strong>Conclusions: </strong>We conclude that circRbfox1 serves as pain regulator in diabetic colonic hypersensitivity and provides a potential therapeutic target in clinic.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":"e70896"},"PeriodicalIF":5.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758128","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}