Translational Stroke Research最新文献

{"title":"Correction to: Global and Regional Burden of Ischemic Stroke Disease from 1990 to 2021: An Age‑Period‑Cohort Analysis.","authors":"Weimin Zhu, Xiaxia He, Daochao Huang, Yiqing Jiang, Weijun Hong, Shaofa Ke, En Wang, Feng Wang, Xianwei Wang, Renfei Shan, Suzhi Liu, Yinghe Xu, Yongpo Jiang","doi":"10.1007/s12975-025-01325-5","DOIUrl":"10.1007/s12975-025-01325-5","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1921"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombectomy in Stroke Patients with Large Vessel Occlusion and Mild Symptoms: Insights from a Multicenter Observational Study.","authors":"Kai Qiu, Yu Hang, Penghua Lv, Ying Liu, Mingchao Li, Liandong Zhao, Qijin Zhai, Jinan Chen, Zhenyu Jia, Yuezhou Cao, Linbo Zhao, Haibin Shi, Sheng Liu","doi":"10.1007/s12975-025-01337-1","DOIUrl":"10.1007/s12975-025-01337-1","url":null,"abstract":"<p><p>To evaluate whether endovascular thrombectomy (EVT) combined with best medical management (BMM) is more effective than BMM alone in treating mild stroke patients (National Institutes of Health Stroke Scale score < 6) with large vessel occlusion (LVO). A multicentric retrospective cohort of patients with LVO and mild stroke within 24 h from symptom onset was included. Patients were divided into the primary EVT (EVT_pri) group and the primary BMM (BMM_pri) group according to the treatment strategy. Functional outcomes were compared after propensity score matching. Additionally, adjusted logistic regression analysis was used to assess the association between treatment strategy and functional outcomes. Finally, 419 patients were included, with 137 receiving EVT_pri and 282 receiving BMM_pri. After propensity score matching (EVT_pri, 126 vs. BMM_pri, 126), baseline characteristics were balanced between the two groups. No significant difference was observed in 3-month functional independence (modified Rankin Scale [mRS] 0-2, 78.6% vs. 76.2%. In the overall cohort, EVT_pri was not associated with functional independence (adjusted odds ratio [aOR], 0.87; 95% confidence interval [CI], 0.43-1.47). However, patients in the EVT_pri group were more likely to experience symptomatic intracranial hemorrhage (aOR, 1.27; 95% CI, 1.05-1.89). Subgroup analysis revealed that EVT_pri was significantly associated with functional independence in vertebrobasilar occlusion subgroup (aOR, 1.78; 95% CI, 1.20-3.90). Our findings did not support the systematic use of EVT for mild stroke with LVO, except in cases of vertebrobasilar occlusion, which may represent a subgroup where EVT_pri could provide significant benefits.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1644-1654"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobiomodulation Promotes Early Recovery of Olfactory Function and Modulates Neuroprotective Gene Expression in a Mouse Model of Ischemic Stroke.","authors":"Reham A Shalaby, Acquah Emmanuel, Fatemeh Dehgan Nezhad, Kohinur Akter, S M Abdus Salam, Jawoon Yi, Sang Seong Kim, Jihwan Park, Hyuk Sang Kwon, Kyung Hwa Lee, Young Ro Kim, Euiheon Chung","doi":"10.1007/s12975-025-01343-3","DOIUrl":"10.1007/s12975-025-01343-3","url":null,"abstract":"<p><p>Ischemic stroke often leads to neurological deficits, including olfactory dysfunction, which can significantly diminish quality of life. Photobiomodulation (PBM) has emerged as a promising therapeutic strategy for enhancing post-stroke recovery, although the molecular mechanisms, particularly regarding gene expression change, are not yet fully understood. This study investigates the long-term effects of photothrombosis (PT) on olfactory function and the olfactory bulb (OB) microenvironment, with a focus on PBM's efficacy during both early and late phases. In a mouse OB PT stroke model, PBM therapy (808-nm laser, 40 J/cm² fluence, 325 mW/cm², 2 min daily) was applied from day 2 to day 7 post-PT. Olfactory function was monitored from pre-stroke through day 28 using the buried food test (BFT), and MRI scans were performed on days 7 and 28 to assess tissue damage. RNA sequencing (RNA-seq) and reverse transcription quantitative PCR (RT-qPCR) were conducted on day 7 to evaluate gene expression changes, with additional RT-qPCR analyses performed on day 28. PBM significantly accelerated olfactory function recovery by day 14, with full recovery maintained through day 28. Despite functional recovery, MRI results indicated persistent infarction at 28 days. RNA-seq identified upregulation of neuroprotective genes, including Gpr39 and Or4m1, following PBM treatment, suggesting enhanced gene expression related to acute-phase recovery. However, the impact of PBM on gene expression and functional recovery appeared to wane in the later stages of recovery. These findings underscore PBM's potential to enhance early-stage recovery in ischemic stroke, though its benefits may be more limited in the chronic phase.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1723-1732"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Model Based on Circulating Biomarkers for Discriminating Symptomatic Spontaneous Intracranial Artery Dissection.","authors":"Peng Liu, Xin Nie, Bing Zhao, Jiangan Li, Yisen Zhang, Guibing Wang, Lei Chen, Hongwei He, Shuo Wang, Qingyuan Liu, Jinrui Ren","doi":"10.1007/s12975-024-01322-0","DOIUrl":"10.1007/s12975-024-01322-0","url":null,"abstract":"<p><p>Spontaneous intracranial artery dissection (sIAD) is the leading cause of stroke in young individuals. Identifying high-risk sIAD cases that exhibit symptoms and are likely to progress is crucial for treatment decision-making. This study aimed to develop a model relying on circulating biomarkers to discriminate symptomatic sIADs. The study prospectively collected sIAD tissues and corresponding serums from January 2020 to December 2022 as the discovery cohort. Symptomatic sIADs were defined as those with mass effect, hemorrhagic, or ischemic stroke. A stratification model was developed using the machine-learning algorithm within the derivation cohort (a cross-sectional cohort including from January 2018 to August 2022) and validated within the validation cohort (a longitudinal cohort including from January 2017 to April 2023). In the discovery cohort (n = 10, 5 symptomatic), analyses of tissues and serums revealed 15 proteins and 2 cytokines with significance between symptomatic and asymptomatic sIADs. Among these biomarkers, six proteins and one cytokine, participating in the immune response and inflammatory-related pathways, have a good consistency in expression level between sIAD tissues and serums. In the derivation cohort (n = 181, 77 symptomatic), a model incorporating these 7 biomarkers was highly discriminative of symptomatic sIADs (area under curve [AUC], 0.95). This model performed well in predicting the occurrence of sIAD-related symptoms in the validation cohort (n = 84, 26 symptomatic) with an AUC of 0.88. This study revealed seven circulating biomarkers of symptomatic sIAD and provided a high-accuracy model relying on these circulating biomarkers to identify symptomatic sIADs, which may aid in clinical decision-making for sIADs.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1509-1522"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood-Brain Barrier Permeability.","authors":"Crhistian-Mario Oblitas, Ana Sampedro-Viana, Sabela Fernández-Rodicio, Manuel Rodríguez-Yáñez, Iria López-Dequidt, Arturo Gonzalez-Quintela, Antonio J Mosqueira, Jacobo Porto-Álvarez, Javier Martínez Fernández, Marcos Bazarra-Barreiros, María Teresa Abengoza-Bello, Sara Ortega-Espina, Alberto Ouro, Francisco Campos, Tomás Sobrino, José Castillo, Maria Luz Alonso-Alonso, Pablo Hervella, Ramón Iglesias-Rey","doi":"10.1007/s12975-025-01349-x","DOIUrl":"10.1007/s12975-025-01349-x","url":null,"abstract":"<p><p>Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1783-1791"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes of Stereotactic Radiosurgery Focused Treatment of Brain Arteriovenous Malformations Based on Rupture Status: A Systematic Review and Meta-Analysis.","authors":"Meah T Ahmed, Anand Kaul, Joanna Roy, Basel Musmar, Santiago D Mendoza-Ayús, Morena P Koorie, Cheritesh R Amaravadi, Antony A Fuleihan, Stavropoula I Tjoumakaris, Michael R Gooch, Robert H Rosenwasser, Pascal Jabbour","doi":"10.1007/s12975-025-01339-z","DOIUrl":"10.1007/s12975-025-01339-z","url":null,"abstract":"<p><p>Stereotactic radiosurgery (SRS) is a non-invasive treatment option for brain arteriovenous malformations (bAVMs). However, SRS cures are delayed, making it less favorable for higher risk ruptured bAVMs (rbAVMs) than unruptured (ubAVMs). This systematic review and meta-analysis explores the long-term outcomes of SRS-focused protocols for rbAVMs and ubAVMs. This study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Literature search was conducted using PubMed, Ovid Medline, Scopus, and hand-search on January 30th, 2025. The inclusion criteria encompassed studies: distinguishing cohorts by rupture status, reporting post-SRS outcomes, and without overlapping series. Pooled analysis was performed from 24 articles using DerSimonian-Laird random effects models. Subgroup and meta-regression analyses were also conducted. All analyses were performed using R. For rbAVMs, the pooled rupture, obliteration, and mortality rates were 7.14% (95% CI: 5.76%-8.64%), 65.0% (95% CI: 57.2%-72.4%), and 0.87% (95% CI: 0.00%-5.14%), respectively, and for ubAVMs, 6.13% (95% CI: 4.71%-7.69%), 59.5% (95% CI: 51.3%-67.3%), and 0.89% (95% CI: 0.00%-3.82%), respectively. Subgroup meta-analyses of rupture rates and obliteration rates showed no significant differences based on prior treatments (Q = 2.47, p = 0.48; Q = 4.34, p = 0.23; respectively) or volume-staging protocols (Q = 4.90, p = 0.18; Q = 1.12, p = 0.77, respectively). Meta-regression analysis for rbAVMs demonstrated a positive correlation between intranidal aneurysms and rupture rate (p < 0.05, R² = 100%), an inverse correlation between Spetzler-Martin (SM) grade I-II bAVMs and obliteration rate (p < 0.05, R² = 68.6%), and a positive correlation between SM grade III-V bAVMs and obliteration rate (p < 0.05, R² = 68.0%). Meta-regression analysis for ubAVMs demonstrated an inverse correlation between eloquent-region lesions and rupture rate (p < 0.05, R² = 31.3%), and surprisingly a positive correlation between mean age and obliteration rate (p < 0.05, R² = 23.8%). SRS-focused studies show similar long-term outcomes regardless of rupture status, but presence of underlying factors indicates the need for individualized risk-benefit analysis.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1666-1688"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Biomarkers Related to the Pathogenesis and Prognosis of Pediatric Moyamoya Disease Via Cerebrospinal Fluid Proteomics.","authors":"Youngbo Shim, Seung Ah Choi, Kisoon Dan, Eun Jung Koh, Saehim Ha, Ji Hoon Phi, Joo Whan Kim, Dohyun Han, Seung-Ki Kim","doi":"10.1007/s12975-025-01384-8","DOIUrl":"https://doi.org/10.1007/s12975-025-01384-8","url":null,"abstract":"<p><p>Developing cost-effective, noninvasive biomarker-based tests could transform moyamoya disease (MMD) management. This study aimed to identify clinically relevant cerebrospinal fluid (CSF) biomarkers through comprehensive proteomic screening in a large MMD cohort. CSF protein profiles from 104 MMD patients and 14 non-tumorous hydrocephalus patients were analyzed via liquid chromatography-tandem mass spectrometry. Enrichment analysis was conducted on canonical pathways and differentially expressed proteins (DEPs). The protein-protein interaction network data included all proteins involved in canonical pathways. Potential markers were validated via ELISA. Weighted gene coexpression network analysis (WGCNA) revealed clinical factor-related modules. We identified 2463 proteins, and 2307 were quantified in at least one sample. A total of 321 significant DEPs were identified, with 8 proteins upregulated and 11 proteins downregulated in MMD samples. ELISA confirmed the increased expression of ALB and SLITRK1. WGCNA revealed seven modules correlated with clinical factors, linking preoperative cerebral infarction to the module eigengene (ME) red module and favorable modified Rankin scale scores to the MEblack module. BASP1 and LDHA were significantly upregulated in MEred, whereas CD9 and EMILIN1 were upregulated in MEblack. Our findings shed light on the proteomics of CSF from MMD patients, identifying potential novel biomarkers such as SLITRK1 and markers of preoperative cerebral infarction (BASP1, LDHA) and clinical outcome (CD9, EMILIN1). These markers have potential as new diagnostic and therapeutic targets for MMD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial Cell Reprogramming in Ischemic Stroke: A Review of Recent Advancements and Translational Challenges.","authors":"Andrei Greșiță, Dirk M Hermann, Ianis Kevyn Stefan Boboc, Thorsten R Doeppner, Eugen Petcu, Ghinea Flavia Semida, Aurel Popa-Wagner","doi":"10.1007/s12975-025-01331-7","DOIUrl":"10.1007/s12975-025-01331-7","url":null,"abstract":"<p><p>Ischemic stroke, the second leading cause of death worldwide and the leading cause of long-term disabilities, presents a significant global health challenge, particularly in aging populations where the risk and severity of cerebrovascular events are significantly increased. The aftermath of stroke involves neuronal loss in the infarct core and reactive astrocyte proliferation, disrupting the neurovascular unit, especially in aged brains. Restoring the balance between neurons and non-neuronal cells within the perilesional area is crucial for post-stroke recovery. The aged post-stroke brain mounts a fulminant proliferative astroglial response, leading to gliotic scarring that prevents neural regeneration. While countless therapeutic techniques have been attempted for decades with limited success, alternative strategies aim to transform inhibitory gliotic tissue into an environment conducive to neuronal regeneration and axonal growth through genetic conversion of astrocytes into neurons. This concept gained momentum following discoveries that in vivo direct lineage reprogramming in the adult mammalian brain is a feasible strategy for reprogramming non-neuronal cells into neurons, circumventing the need for cell transplantation. Recent advancements in glial cell reprogramming, including transcription factor-based methods with factors like NeuroD1, Ascl1, and Neurogenin2, as well as small molecule-induced reprogramming and chemical induction, show promise in converting glial cells into functional neurons. These approaches leverage the brain's intrinsic plasticity for neuronal replacement and circuit restoration. However, applying these genetic conversion therapies in the aged, post-stroke brain faces significant challenges, such as the hostile inflammatory environment and compromised regenerative capacity. There is a critical need for safe and efficient delivery methods, including viral and non-viral vectors, to ensure targeted and sustained expression of reprogramming factors. Moreover, addressing the translational gap between preclinical successes and clinical applications is essential, emphasizing the necessity for robust stroke models that replicate human pathophysiology. Ethical considerations and biosafety concerns are critically evaluated, particularly regarding the long-term effects and potential risks of genetic reprogramming. By integrating recent research findings, this comprehensive review provides an in-depth understanding of the current landscape and future prospects of genetic conversion therapy for ischemic stroke rehabilitation, highlighting the potential to enhance personalized stroke management and regenerative strategies through innovative approaches.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1811-1835"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke.","authors":"Xinyuan Yu, Lihong Dang, Ashis Dhar, Ran Zhang, Feng Xu, Ivan Spasojevic, Huaxin Sheng, Wei Yang","doi":"10.1007/s12975-025-01351-3","DOIUrl":"10.1007/s12975-025-01351-3","url":null,"abstract":"<p><p>Ischemic stroke disrupts protein homeostasis in brain cells, causes endoplasmic reticulum (ER) stress, and consequently activates the unfolded protein response (UPR). The primary function of UPR activation is to help cells restore ER function, thereby promoting cell survival. A major adaptive UPR branch is mediated by activating transcription factor 6 (ATF6). We previously provided experimental evidence that activation of ATF6 signaling in neurons improves short-term outcome after both transient and permanent stroke. However, the effect of ATF6 activation in astrocytes on stroke outcome remains undetermined, and critically, the long-term therapeutic potential of targeting this UPR branch in permanent stroke has not been evaluated. The current study aimed to address these two critical unknowns. First, using conditional knock-in mice in which functional short-form ATF6 (sATF6) is specifically expressed in astrocytes, we demonstrated that astrocytic ATF6 activation modestly improved outcome after permanent stroke. Then, our pharmacokinetic analysis indicated that compound AA147, an ATF6-specific activator, can cross the blood-brain barrier. Lastly, we found that post-stroke treatment with AA147 had no significant beneficial effect on short-term outcome, but improved long-term functional recovery in both young and aged mice after permanent stroke. Together with previous findings, our data support the notion that the ATF6 pathway is a promising target for stroke therapy.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1799-1810"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke.","authors":"Huiran Zhang, Yanfei Tian, Yan Zhang, Yan Wang, Jinlong Qi, Xiangyu Wang, Yi Yuan, Rong Chen, Yupeng Zhao, Chang Liu, Najing Zhou, Lanxin Liu, Han Hao, Xiaona Du, Hailin Zhang","doi":"10.1007/s12975-025-01329-1","DOIUrl":"10.1007/s12975-025-01329-1","url":null,"abstract":"<p><p>Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential. Transient or distal middle cerebral artery occlusion model was established with C57 mouse to evaluate the role of QO-83. Solitary dose of QO-83 contributes to the microglia inhibition and fibrotic scar mitigation post stroke. QO83 shows prominent effect on reducing infarction area, alleviating cerebral edema, maintaining blood-brain barrier integrity, and enhancing neurogenesis. Single-nucleus RNA sequencing unveils neuroprotection and specific microglial subclusters influenced by QO-83. More importantly, QO83 shows promise in enhancing survival rates with dose dependence. Notably, these protective effects extend beyond the 4-6 h post-reperfusion window. Additionally, continuous dosing of QO-83 correlates with enhanced cognition. In conclusion, this study highlights QO-83 as a protective agent against ischemic brain injury, showcasing its multifaceted effects and potential as a therapeutic strategy.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1577-1593"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}