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Translational Insights Into Pericyte-Mediated Regulation of Cerebral Blood Flow: Implications for Ischemic Stroke. 周细胞介导的脑血流调节的翻译见解:对缺血性卒中的影响。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-06-25 DOI: 10.1161/STROKEAHA.125.052018
Yi-Jia Fangma, Zhu-Chen Zhou, Zhong Chen, Yan-Rong Zheng
{"title":"Translational Insights Into Pericyte-Mediated Regulation of Cerebral Blood Flow: Implications for Ischemic Stroke.","authors":"Yi-Jia Fangma, Zhu-Chen Zhou, Zhong Chen, Yan-Rong Zheng","doi":"10.1161/STROKEAHA.125.052018","DOIUrl":"10.1161/STROKEAHA.125.052018","url":null,"abstract":"<p><p>Microvascular reperfusion stands as a critical therapeutic objective in ischemic stroke management. Pericytes, specialized contractile mural cells enveloping cerebral capillaries, serve as master regulators of capillary tone and regional hemodynamics, exerting a profound influence on post-ischemic stroke blood flow dynamics. Despite their pivotal role in microcirculatory control, there are limited therapeutic targets specifically aimed at regulating their activity. Here, we summarize the multifaceted roles of pericytes in ischemic stroke and discuss various pericyte-related strategies for ischemic stroke. While these interventions offer some benefits, they also present notable limitations, including adverse reactions, structural instability, suboptimal efficacy, and challenges in clinical translation. Future efforts directed toward deciphering the spatiotemporal responses of pericytes across different ischemic phases and achieving their selective and effective regulation are expected to yield novel strategies for precision microcirculatory rehabilitation.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"e254-e266"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute Cortical Stroke Alters Neural Activity in Subthalamic Nucleus, Which Correlates With Motor Disability in Rats. 急性皮质性中风改变大鼠丘脑底核神经活动,与运动障碍相关。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-08-12 DOI: 10.1161/STROKEAHA.125.051265
Zhengdao Deng, Myles Mc Laughlin, Ugur Kilic, Boateng Asamoah, Bart Nuttin
{"title":"Acute Cortical Stroke Alters Neural Activity in Subthalamic Nucleus, Which Correlates With Motor Disability in Rats.","authors":"Zhengdao Deng, Myles Mc Laughlin, Ugur Kilic, Boateng Asamoah, Bart Nuttin","doi":"10.1161/STROKEAHA.125.051265","DOIUrl":"10.1161/STROKEAHA.125.051265","url":null,"abstract":"<p><strong>Background: </strong>The subthalamic nucleus (STN) plays a role in motor control, yet it is unclear whether acute cortical stroke (ACS) causes abnormal STN activity and neural oscillations. Moreover, the correlation between these subthalamic neurophysiological changes and motor disability remains unknown. To address this, we studied the impact of ACS on neural activity in the STN. We then examined the correlation between changes in STN activity and motor disability.</p><p><strong>Methods: </strong>Fifty-six Sprague-Dawley rats were used. Although rats were anesthetized, we inserted electrodes in the STN and induced an ACS by creating a photothrombotic lesion in the ipsilateral motor cortex. Local field potentials were recorded before and after ACS. The motor behavior was assessed before and after ACS using a single-pellet reaching task.</p><p><strong>Results: </strong>Rats experienced significant motor disability after ACS. STN firing rate significantly decreased after ACS. Additionally, delta (0.5-4 Hz) and gamma (80-130 Hz) power significantly decreased after ACS. Furthermore, the decrease in delta mean power correlated with decreases in success rate (<i>r</i>=0.77; <i>P</i>=0.009) and first try success rate (<i>r</i>=0.69; <i>P</i>=0.028). The decreases in gamma mean power (<i>r</i>=0.68; <i>P</i>=0.029) and gamma peak power (<i>r</i>=0.74; <i>P</i>=0.015) correlated with the decrease in success rate. The decrease in gamma power significantly correlated with the decreased STN firing rate. However, decreased delta power exhibited no correlation with decreased gamma power.</p><p><strong>Conclusions: </strong>Our study provides the first evidence that ACS causes significant subthalamic inhibition and abnormal oscillatory activity in rats, with these effects significantly correlated with motor disability. Notably, these abnormal STN oscillations serve as a predictive biomarker for motor disability during the acute phase of cortical stroke. Furthermore, our findings highlight the potential of neuromodulation strategies to mitigate poststroke motor disability by targeting and reducing abnormal STN activity.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"3060-3071"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822654","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}
引用次数: 0
MRI-Based Classification of Cerebral Hemodynamic Failure With Resting Perfusion Metrics and Cerebrovascular Reactivity. 基于静息灌注指标和脑血管反应性的脑血流动力学衰竭mri分类。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1161/STROKEAHA.125.050978
Ece Su Sayin, James Duffin, Julien Poublanc, Joseph A Fisher, David J Mikulis, Olivia Sobczyk
{"title":"MRI-Based Classification of Cerebral Hemodynamic Failure With Resting Perfusion Metrics and Cerebrovascular Reactivity.","authors":"Ece Su Sayin, James Duffin, Julien Poublanc, Joseph A Fisher, David J Mikulis, Olivia Sobczyk","doi":"10.1161/STROKEAHA.125.050978","DOIUrl":"10.1161/STROKEAHA.125.050978","url":null,"abstract":"<p><strong>Background: </strong>The inability to augment regional cerebral blood flow (CBF) in the setting of steno-occlusive disease involving large brain-supplying arteries is a risk factor for stroke. The gold standard for detecting such hemodynamic impairment requires the application of a vasodilatory stimulus while measuring changes in CBF. Resting blood flow metrics derived from computed tomography or magnetic resonance imaging (MRI) perfusion methods have been applied as surrogates for assessing hemodynamic insufficiency including relative CBF, relative cerebral blood volume, and mean transit time (MTT). The purpose of this study, therefore, was to compare the sensitivity and specificity of MRI resting perfusion metrics with cerebrovascular reactivity (CVR). MRI CVR mapping was used as a reference standard for comparing MRI perfusion-derived CBF, CBV, and MTT.</p><p><strong>Methods: </strong>MRI resting perfusion metrics were measured using a recently reported noninvasive method that induces a bolus of hypoxia-induced deoxyhemoglobin as the dynamic susceptibility contrast in place of the gadolinium-based contrast agents. CVR was measured using a standardized hypercapnic vasoactive stimulus during blood oxygen level-dependent MRI as a surrogate for CBF.</p><p><strong>Results: </strong>Twenty-two patients with large artery steno-occlusive disease (mean age±SD, 46±17.8 years; 60% female), 24 healthy participants for the CVR atlas (35.1±13.8 years; 33% female), and 25 for the perfusion atlas (38.4±17.6 years; 24% female) were recruited. Significant differences in mean hemispheric middle cerebral artery perfusion (MTT, relative CBF) and CVR metrics in gray matter (<i>P</i><0.05) were observed between patients and healthy participants. Comparisons between affected and unaffected hemispheres in patients showed significant differences only for MTT and CVR in gray matter (<i>P</i><0.05). Receiver-operating characteristic curves identified CVR as the most sensitive predictor for hemodynamic impairment followed by MTT.</p><p><strong>Conclusions: </strong>CVR remains a more accurate test for assessing hemodynamic impairment compared to resting blood flow metrics.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"3034-3046"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CASCOM Study: CAR Score Predicting Restroke in Symptomatic Carotid Stenosis With Only Intensive Medical Therapy. CASCOM研究:CAR评分预测症状性颈动脉狭窄患者仅接受强化药物治疗再卒中
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1161/STROKEAHA.125.052151
Saeid Shahidi, Troels Wienecke, Emilie Noeddeskov Eilersen, Magdalena Broda, Anna Pelta, Stefan Andreas Zambach
{"title":"CASCOM Study: CAR Score Predicting Restroke in Symptomatic Carotid Stenosis With Only Intensive Medical Therapy.","authors":"Saeid Shahidi, Troels Wienecke, Emilie Noeddeskov Eilersen, Magdalena Broda, Anna Pelta, Stefan Andreas Zambach","doi":"10.1161/STROKEAHA.125.052151","DOIUrl":"10.1161/STROKEAHA.125.052151","url":null,"abstract":"<p><strong>Background: </strong>Carotid endarterectomy for symptomatic carotid stenosis is based on decades-old trials, while modern medical therapy has substantially improved outcomes. The carotid artery risk (CAR) score predicts stroke risk using clinical and imaging factors. This study evaluates the 2-year risk of recurrent ipsilateral stroke in patients with recent transient ischemic attack, amaurosis fugax, or minor stroke and ipsilateral symptomatic carotid stenosis treated with intensive medical therapy.</p><p><strong>Methods: </strong>In this prospective, single-arm observational study conducted in Denmark from October 2020 to March 2023, we enrolled 109 patients with recent TIA, amaurosis fugax, or minor stroke and 50% to 99% ipsilateral symptomatic carotid stenosis. Patients with a CAR score ≤20% or >20%, as well as those with contraindications to surgery, were included. All received intensive medical therapy. The primary outcome was ipsilateral recurrent stroke or death within 2 years.</p><p><strong>Results: </strong>The mean age was 73 years; 60% were male patients. Six patients (5.5%) experienced ipsilateral recurrent stroke, representing a ≈75% reduction compared with historical NASCET (North American Symptomatic Carotid Endarterectomy Trial) rates (≈23%). Patients with CAR score ≤20% (n=96) had a significantly lower 2-year stroke rate (3.1%) than those with CAR score >20% (n=13; 23%; <i>P</i>=0.02). The CAR score ≤20% subgroup showed high predictive accuracy: sensitivity of 0.90, specificity of 0.50, and positive predictive value of 0.97.</p><p><strong>Conclusions: </strong>In this observational study, modern medical therapy was associated with low rates of recurrent stroke in patients with symptomatic carotid stenosis. Patients with a CAR score ≤20% had a very low risk of recurrent stroke, suggesting that selected patients may be managed conservatively.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"3072-3077"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection. 缺血性卒中中的脑-体相互作用:VNS重编程小胶质细胞和FNS增强小脑神经保护。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-06-25 DOI: 10.1161/STROKEAHA.125.051470
Yuchun Wang, Zhe Yang, Jinling Wang, Minyan Ge, Nianhong Wang, Shumao Xu
{"title":"Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection.","authors":"Yuchun Wang, Zhe Yang, Jinling Wang, Minyan Ge, Nianhong Wang, Shumao Xu","doi":"10.1161/STROKEAHA.125.051470","DOIUrl":"10.1161/STROKEAHA.125.051470","url":null,"abstract":"<p><p>Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS's excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"e267-e278"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tadalafil Treatment in Patients With Cerebral Small Vessel Disease: The ETLAS-2 Randomized Clinical Trial. 他达拉非治疗脑血管病患者:ETLAS-2随机临床试验
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-07-28 DOI: 10.1161/STROKEAHA.125.051602
Joakim Ölmestig, Kristian Nygaard Mortensen, Marie Bjerregaard Thomas, Birgitte Fagerlund, Nadia Naveed, Mette Maria Nordling, Marie Katrine Klose Nielsen, Brian Schou Rasmussen, Hanne Christensen, Helle Klingenberg Iversen, Mai Bang Poulsen, Hartwig Roman Siebner, Christina Kruuse
{"title":"Tadalafil Treatment in Patients With Cerebral Small Vessel Disease: The ETLAS-2 Randomized Clinical Trial.","authors":"Joakim Ölmestig, Kristian Nygaard Mortensen, Marie Bjerregaard Thomas, Birgitte Fagerlund, Nadia Naveed, Mette Maria Nordling, Marie Katrine Klose Nielsen, Brian Schou Rasmussen, Hanne Christensen, Helle Klingenberg Iversen, Mai Bang Poulsen, Hartwig Roman Siebner, Christina Kruuse","doi":"10.1161/STROKEAHA.125.051602","DOIUrl":"10.1161/STROKEAHA.125.051602","url":null,"abstract":"<p><strong>Background: </strong>White matter hyperintensities and reduced cerebral blood flow are hallmarks of cerebral small vessel disease (CSVD). We tested the feasibility of daily treatment with the vasoactive drug tadalafil in patients with CSVD and its effects on cognition and imaging markers of CSVD.</p><p><strong>Methods: </strong>The ETLAS-2 trial (Effect of Tadalafil in Lacunar Stroke) was a randomized, placebo-controlled, double-blind, parallel phase II trial testing 3 months of daily tadalafil 20 mg versus placebo in patients with CSVD and previous stroke or transient ischemic attack. Participants were included from the Capital Region of Denmark from 2022 to 2024. Outcomes were assessed at baseline and after 3 months. A binary logistic regression model with the treatment group as a covariate was used to calculate the primary outcome of feasibility (≥90% study drug compliance). Secondary outcomes included the Montreal Cognitive Assessment, magnetic resonance imaging markers of CSVD (Standards for Reporting Vascular Changes on Neuroimaging criteria), blood pressure, and adverse events.</p><p><strong>Results: </strong>We included 76 participants (20 female, mean age, 68.0±8.9 years). Seventy-one initiated treatment, and 26 of 38 participants with tadalafil were ≥90% compliant versus 31 of 33 with placebo (odds ratio, 0.13 [95% CI, 0.03-0.69]; <i>P</i>=0.030). There was a female preponderance in tadalafil dropouts, with 46% of females stopping treatment, compared with only 16% of males. Adverse events occurred in 76% of participants with tadalafil versus 36% with placebo (odds ratio, 5.49 [95% CI, 1.81-18.07]; <i>P</i>=0.001). A trend toward lower white matter hyperintensity volume at follow-up was observed in the tadalafil group in the unadjusted per-protocol analysis (relative change, 0.939 [95% CI, 0.881-1.001]; <i>P</i>=0.054). No differences were observed in cognition, mental well-being, or blood pressure.</p><p><strong>Conclusions: </strong>In participants with CSVD, adherence to tadalafil was significantly lower than to placebo and did not meet the prespecified compliance threshold. We observed a nonsignificant reduction in white matter hyperintensity volume after tadalafil, which warrants larger and prolonged studies with reduced tadalafil doses to explore potential benefits in CSVD.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT05173896.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"2846-2857"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733258","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}
引用次数: 0
Effect of LDL-Cholesterol Levels and Oral Atorvastatin on Outcomes After Pipeline Therapy for Intracranial Aneurysms. ldl -胆固醇水平及口服阿托伐他汀对颅内动脉瘤管道治疗后预后的影响。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1161/STROKEAHA.124.049833
Xin Feng, Chi Huang, Xin Tong, Zhuohua Wen, Yajun Zhu, Mengshi Huang, Jiancheng Lin, Jiwan Huang, Hao Yuan, Anqi Xu, Gengwu Ma, Runze Ge, Can Li, Chao Peng, Shixing Su, Xin Zhang, Xifeng Li, Zongduo Guo, Aihua Liu, Chuanzhi Duan
{"title":"Effect of LDL-Cholesterol Levels and Oral Atorvastatin on Outcomes After Pipeline Therapy for Intracranial Aneurysms.","authors":"Xin Feng, Chi Huang, Xin Tong, Zhuohua Wen, Yajun Zhu, Mengshi Huang, Jiancheng Lin, Jiwan Huang, Hao Yuan, Anqi Xu, Gengwu Ma, Runze Ge, Can Li, Chao Peng, Shixing Su, Xin Zhang, Xifeng Li, Zongduo Guo, Aihua Liu, Chuanzhi Duan","doi":"10.1161/STROKEAHA.124.049833","DOIUrl":"10.1161/STROKEAHA.124.049833","url":null,"abstract":"<p><strong>Background: </strong>We aimed to determine the effects of statin treatment on outcomes of pipeline embolization device therapy for intracranial aneurysms in relation to LDL (low-density lipoprotein) cholesterol levels.</p><p><strong>Methods: </strong>Using data from the SESIA registry (Safety and Efficacy of Stent Deployment for Intracranial Aneurysms), we enrolled participants who underwent pipeline embolization device implantation at 4 centers in China (2018-2022). Statin users (atorvastatin 20 mg daily, for ≥3 days and ≥6 months preprocedurally and postprocedurally, respectively) were matched with nonstatin users (1:1) using propensity scores and further adjusted by inverse probability of treatment weighting, balancing for baseline characteristics, procedural details, and lipid levels (based on East Asian profiles). Study outcomes include perioperative complications, aneurysmal occlusion, in-stent stenosis, and clinical prognosis at the latest follow-up. Multivariable analyses using logistic and Cox regression models adjusted for these factors in both prematched and postmatched cohorts, evaluating the role of lipid modification in subgroups.</p><p><strong>Results: </strong>Of the 1558 patients screened, 1193 (53.75±11.07 years, 69.4% females; statin: n=603, nonstatin: n=590) were enrolled with 3- to 48-month follow-up. In the matched cohort (352 pairs), statin treatment reduced the incidences of perioperative cerebrovascular (2.0% versus 8.5%, <i>P</i>=0.001) and follow-up ischemic (1.7% versus 5.1%, <i>P</i>=0.020) complications. Multivariable analyses in participants with baseline LDL-cholesterol ≥2.59 mmol/L showed that statin treatment was associated with fewer perioperative cerebrovascular complications (odds ratio, 0.371 [95% CI, 0.195-0.705]; <i>P</i>=0.002), in-stent stenosis (hazard ratio, 0.433 [95% CI, 0.269-0.698]; <i>P</i>=0.001), and follow-up ischemic events (hazard ratio, 0.315 [95% CI, 0.135-0.733]; <i>P</i>=0.007; <i>P</i> values for interaction were 0.671, 0.009, and 0.507, respectively, versus <2.59 mmol/L). Postmatched analyses confirmed consistency for perioperative cerebrovascular complications (odds ratio, 0.416 [95% CI, 0.211-0.821]), in-stent stenosis (hazard ratio, 0.397 [95% CI, 0.232-0.667]), and follow-up ischemic events (hazard ratio, 0.364 [95% CI, 0.148-0.895]).</p><p><strong>Conclusions: </strong>Atorvastatin treatment improved postpipeline embolization device-deployment outcomes by reducing ischemic events, particularly in patients with elevated LDL-cholesterol. The long-term benefits of adjunctive statin use in this population warrant further investigation.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03387995.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"3002-3013"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790113","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}
引用次数: 0
Direct Endovascular Versus Bridging Therapy in M2 Segment Occlusion of Middle Cerebral Artery: A MR CLEAN Registry Study. 直接血管内与桥接治疗大脑中动脉M2段闭塞:MR CLEAN登记研究。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-08-29 DOI: 10.1161/STROKEAHA.125.051967
Mohamed F Doheim, Robrecht R M M Knapen, Julie Staals, Wouter J Schonewille, Diederik W J Dippel, Adriaan C G M van Es, Hester F Lingsma, Christiaan van der Leij, Charles B Majoie, Raul G Nogueira, Robert J van Oostenbrugge, Wim H van Zwam
{"title":"Direct Endovascular Versus Bridging Therapy in M2 Segment Occlusion of Middle Cerebral Artery: A MR CLEAN Registry Study.","authors":"Mohamed F Doheim, Robrecht R M M Knapen, Julie Staals, Wouter J Schonewille, Diederik W J Dippel, Adriaan C G M van Es, Hester F Lingsma, Christiaan van der Leij, Charles B Majoie, Raul G Nogueira, Robert J van Oostenbrugge, Wim H van Zwam","doi":"10.1161/STROKEAHA.125.051967","DOIUrl":"10.1161/STROKEAHA.125.051967","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The optimal strategy for managing M2 segment occlusions of the middle cerebral artery, whether with direct endovascular treatment (EVT) or bridging therapy with intravenous thrombolysis (IVT) before EVT, remains unclear. This study aimed to evaluate the effectiveness and safety of both approaches.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients with M2 segment occlusions of the middle cerebral artery, treated between March 2014 and December 2018, were identified from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a prospective, nationwide, multicenter registry of patients with acute ischemic stroke who underwent endovascular treatment during that period. They were divided into 2 groups: those who received IVT followed by EVT, and those who received EVT alone. Primary outcomes included functional outcomes at 90 days, assessed by ordinal logistic regression analysis of modified Rankin Scale (mRS) scores. Secondary outcomes included recanalization rates measured by extended Thrombolysis in Cerebral Infarction scores, dichotomized mRS scores (0-1, 0-2, and 0-3), death at 90 days, and symptomatic intracranial hemorrhage. All analyses were performed using both unadjusted and adjusted multivariable approaches, with adjustment achieved through inverse probability of treatment weighting to account for baseline imbalances, including age, baseline National Institutes of Health Stroke Scale score, prior stroke, history of atrial fibrillation, anticoagulant use, and transfer status.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 539 patients with M2 occlusions were included in the analysis: 377 received IVT+EVT and 162 received EVT alone. The median age was significantly lower in the IVT+EVT group compared with the EVT-alone group (71 [61-79] versus 74 [65-81]; &lt;i&gt;P&lt;/i&gt;=0.01), whereas the proportion of male patients was similar between groups (55.2% versus 51.9%; &lt;i&gt;P&lt;/i&gt;=0.15). At 90 days, inverse probability of treatment weighting analysis showed that IVT+EVT was significantly associated with reduced disability compared with EVT alone (adjusted common odds ratio for mRS score, 1.52 [95% CI, 1.04-2.21]; &lt;i&gt;P&lt;/i&gt;=0.03). Dichotomized functional outcomes and mortality were numerically in favor of IVT+EVT, with higher rates of mRS score of 0 to 1 (38.9% versus 29.7%, aOR, 1.40 [95% CI, 0.85-2.30]; &lt;i&gt;P&lt;/i&gt;=0.19), mRS score of 0 to 2 (57.8% versus 46.5%; aOR, 1.42 [95% CI, 0.88-2.29]; &lt;i&gt;P&lt;/i&gt;=0.15), and mRS score of 0 to 3 (73.2% versus 59.4%, aOR, 1.54 [95% CI, 0.94-2.51]; &lt;i&gt;P&lt;/i&gt;=0.09), as well as lower 90-day mortality (17.2% versus 25.8%; aOR, 0.83 [95% CI, 0.47-1.45]; &lt;i&gt;P&lt;/i&gt;=0.51). In contrast, recanalization rates and symptomatic intracranial hemorrhage were numerically in favor of EVT alone, but all these differences were not statistically significant (&lt;i&gt;P&lt;/i&gt;&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Bridging therapy may yield superior functio","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"2866-2878"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969681","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}
引用次数: 0
Blood Biospecimen Recommendations for Research on Stroke Outcomes and Recovery. 血液生物标本对中风预后和康复研究的建议。
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-09-22 DOI: 10.1161/STROKEAHA.125.050793
Robynne G Braun, Matthew A Edwardson, Chad M Aldridge, Steven C Cramer, Carlos Cruchaga, Stefan T Engelter, Jin-Moo Lee, Jane M Maguire, Tara M Stanne, Boryana Stamova, Christopher Traenka, Cristina Gallego-Fabrega, Israel Fernandez Cadenas, Arne G Lindgren
{"title":"Blood Biospecimen Recommendations for Research on Stroke Outcomes and Recovery.","authors":"Robynne G Braun, Matthew A Edwardson, Chad M Aldridge, Steven C Cramer, Carlos Cruchaga, Stefan T Engelter, Jin-Moo Lee, Jane M Maguire, Tara M Stanne, Boryana Stamova, Christopher Traenka, Cristina Gallego-Fabrega, Israel Fernandez Cadenas, Arne G Lindgren","doi":"10.1161/STROKEAHA.125.050793","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.050793","url":null,"abstract":"<p><p>The impact of trait-associated genetic variants on stroke risk is by now a well-established area of research that has continued to accelerate since the introduction of genome-wide technologies. More recently, the field has seen an increasing interest in the biology of stroke recovery. Studies designed to evaluate stroke recovery have unique needs that differ from those in studies of stroke risk and acute stroke outcomes. Here we outline the essential considerations for researchers aiming to develop or contribute to blood biomarker research on stroke recovery. Our recommendations incorporate the latest evidence and technologies that have emerged since the prior International Stroke Genetics Consortium Global Alliance recommendations were published in 2015. Nominated contributors with expertise in stroke recovery and genomics met over the course of 9 months and defined the scope of topics, discussed current practice and standards, and revised the recommendations to reflect consensus achieved through 2 rounds of anonymized surveys. Our writing group defined an updated and expanded set of recommendations applicable to a range of research priorities including (1) elucidating the biology of stroke recovery, (2) determining genetic variations associated with good versus poor stroke outcomes and recovery, (3) identifying druggable (or otherwise therapeutically actionable) gene or protein targets for enhanced recovery, and (4) identifying blood biomarkers that can predict stroke outcomes and recovery. The resulting work offers comprehensive guidance on essential preanalytical considerations for blood biomarker studies, encompassing blood collection timing, specimen processing and storage procedures, and regulatory aspects such as informed consent and data sharing. These guidelines will enable the consistent collection of human data on recovery biology at scale, providing the foundational evidence necessary to drive subsequent clinical translation.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"56 10","pages":"e279-e290"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypertension Is Associated With Earlier Onset of Nontraumatic Subarachnoid Hemorrhage in Women: A Mendelian Randomization Study. 高血压与女性非外伤性蛛网膜下腔出血早发相关:孟德尔随机研究
IF 8.9 1区 医学
Stroke Pub Date : 2025-10-01 Epub Date: 2025-07-23 DOI: 10.1161/STROKEAHA.124.047631
Kevin N Vanent, Thabele M Leslie-Mazwi, Charles C Matouk, Kevin N Sheth, Michael R Levitt, Guido J Falcone
{"title":"Hypertension Is Associated With Earlier Onset of Nontraumatic Subarachnoid Hemorrhage in Women: A Mendelian Randomization Study.","authors":"Kevin N Vanent, Thabele M Leslie-Mazwi, Charles C Matouk, Kevin N Sheth, Michael R Levitt, Guido J Falcone","doi":"10.1161/STROKEAHA.124.047631","DOIUrl":"10.1161/STROKEAHA.124.047631","url":null,"abstract":"<p><strong>Background: </strong>Nontraumatic subarachnoid hemorrhage (SAH) is linked to hypertension, a condition highly influenced by common genetic variants. For complex diseases affected by genetic and environmental factors, genetic predisposition plays a key role in early onset. We hypothesize that elevated polygenic susceptibility to hypertension is associated with a younger age of onset in SAH.</p><p><strong>Methods: </strong>We performed a case-only genetic analysis using data from the UK Biobank, a large cohort study that enrolled over 500 000 Britons aged 40 to 69 years between 2006 and 2010. Participants of European ancestry with a known diagnosis of SAH were included, which was ascertained through an algorithmic combination of coded information from baseline in-person interviews and electronic health records. We constructed a polygenic risk score using 817 independent genetic variants associated with higher systolic blood pressure. Participants were categorized into 3 groups: low (polygenic risk score <20 percentile), intermediate (polygenic risk score 20-80 percentile), and high (polygenic risk score >80 percentile) polygenic susceptibility to hypertension. Linear regression was used to assess the relationship between polygenic susceptibility to hypertension and the age of onset of SAH, with multivariable models adjusting for the first 4 genetic principal components, diabetes, and smoking history. Product terms were added to test for interaction with sex. To evaluate causality, we implemented Mendelian randomization analysis using the inverse variance weighted and weighted median methods.</p><p><strong>Results: </strong>We evaluated a total of 1177 SAH cases (mean age of onset, 55 [12] years; female sex, 722 [61.3%]). When evaluating all participants jointly, there was no association between polygenic susceptibility to hypertension and the age of onset of SAH (test-for-trend <i>P</i>=0.13). However, there was a significant interaction between polygenic susceptibility to hypertension and sex (interaction <i>P</i>=0.003): High polygenic susceptibility to hypertension was associated with earlier onset of SAH in female participants only (β, -4.87 [95% CI, -7.59 to -2.15]; test-for-trend <i>P</i><0.001). In Mendelian randomization analysis, each 10 mm Hg increase in genetically determined systolic blood pressure was associated with a 3.6-year earlier onset of SAH in female participants using both the inverse variance weighted (β, -3.59 [95% CI, -5.69 to -1.49]; <i>P</i>=0.001) and weighted median approaches (β, -3.68 [95% CI, -6.99 to -0.37]; <i>P</i>=0.029).</p><p><strong>Conclusions: </strong>Polygenic susceptibility to hypertension is associated with earlier onset of nontraumatic SAH in women. Further studies are needed to replicate these findings in non-European individuals. Genetic predisposition to hypertension could be used for screening and early identification of individuals at risk of SAH.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"2996-3001"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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