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Map3k3  I441M Knock-In Mouse Model of Cerebral Cavernous Malformations.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1161/STROKEAHA.124.049935
Hongyuan Xu, Yingxi Yang, Qiuxia Zhou, Ran Huo, Shaozhi Zhao, Yingfan Sun, Jie Wang, Qiheng He, Qifeng Yu, Jinyi Tang, Yuming Jiao, Jiguang Wang, Yong Cao
{"title":"<i>Map3k3 </i> <sup>I441M</sup> Knock-In Mouse Model of Cerebral Cavernous Malformations.","authors":"Hongyuan Xu, Yingxi Yang, Qiuxia Zhou, Ran Huo, Shaozhi Zhao, Yingfan Sun, Jie Wang, Qiheng He, Qifeng Yu, Jinyi Tang, Yuming Jiao, Jiguang Wang, Yong Cao","doi":"10.1161/STROKEAHA.124.049935","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049935","url":null,"abstract":"<p><strong>Background: </strong>Cerebral cavernous malformations (CCMs) refer to vascular dysplasia primarily found in the brain, affecting ≈0.5% of the population. A somatic <i>Map3k3</i><sup>I441M</sup> mutation has been found in ≈40% of patients with sporadic CCMs, which were typically accompanied by somatic gain-of-function mutations in <i>PIK3CA</i>. Although mouse models of adeno-associated virus-BR1-mediated mutant overexpression have been reported, these models have limitations in representing clinical specimens of CCMs, which typically harbor single allele mutation in <i>Map3k3</i>. A <i>Map3k3</i><sup>I441M</sup> knock-in murine model of CCMs has not yet been established.</p><p><strong>Methods: </strong>The <i>Map3k3</i><sup>I441M</sup> knock-in mice were crossed with <i>Cdh5</i>-creER<sup>T2</sup> mice to induce mutant gene expression specifically in endothelial cells. Subsequently, <i>Map3k3</i><sup>I441M</sup> mice were bred with <i>Pten</i><sup>fl/fl</sup> mice to generate <i>Map3k3</i><sup>I441M</sup>; <i>Pten</i><sup>fl/fl</sup> mice. In both murine models, CCM lesions were examined using magnetic resonance imaging, while single-cell RNA sequencing and immunostaining were utilized to investigate the pathomechanism of the mutation. Finally, we administered an mTOR (mechanistic target of rapamycin) inhibitor to explore its therapeutic effect on lesions of both murine models.</p><p><strong>Results: </strong>Both endothelial <i>Map3k3</i><sup>I441M</sup> mutant juvenile mice and <i>Map3k3</i><sup>I441M</sup>; <i>Pten</i><sup>fl/fl</sup> mice developed abnormal lesions with human CCM characteristics. In <i>Map3k3</i><sup>I441M</sup> mice, the mutant promoted endothelial apoptosis, while activation of the PI3K (phosphatidylinositol 3-kinase) pathway was able to activate the downstream AKT (protein kinase B)/mTOR/p-S6 (phosphorylated S6 ribosomal protein) pathway and upregulate VEGFA (vascular endothelial growth factor A) expression, counteracting apoptosis, and facilitating lesion progression. The activation of PI3K signaling is required for <i>Map3k3</i><sup>I441M</sup> to generate CCM-like lesions in adult mice. Finally, we demonstrated that rapamycin effectively inhibited the formation of lesions in the <i>Map3k3</i><sup>I441M</sup> mice and <i>Map3k3</i><sup>I441M</sup>; <i>Pten</i><sup>fl/fl</sup> mice.</p><p><strong>Conclusions: </strong><i>Map3k3</i><sup>I441M</sup> heterozygous is sufficient to induce lesions in juvenile mice, while the additional activation of PI3K signaling is required for the effective formation of CCMs at the adult stage. The <i>Map3k3</i><sup>I441M</sup> murine model provides a preclinical model for further mechanistic and therapeutic studies of CCMs.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"56 4","pages":"1010-1025"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701211","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
Submaximal Angioplasty for Severe Intracranial Atherosclerotic Stenosis: Benefit of Revascularization at Last.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1161/STROKEAHA.124.049467
Umberto Pensato, Andrew M Demchuk, Geoffrey A Donnan
{"title":"Submaximal Angioplasty for Severe Intracranial Atherosclerotic Stenosis: Benefit of Revascularization at Last.","authors":"Umberto Pensato, Andrew M Demchuk, Geoffrey A Donnan","doi":"10.1161/STROKEAHA.124.049467","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049467","url":null,"abstract":"<p><p>Intracranial atherosclerotic stenosis is a leading cause of stroke with a significant risk of recurrent ischemic events despite aggressive medical management. The longstanding benefits of percutaneous angioplasty and stenting in coronary artery disease, where atherosclerosis is the overarching cause in nearly all cases, provided a compelling rationale for exploring similar interventions in intracranial atherosclerotic stenosis. However, 3 percutaneous angioplasty and stenting randomized trials showed negative or neutral results. The recent BASIS trial (Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis) was the first randomized trial in intracranial atherosclerotic stenosis to demonstrate the benefits of endovascular treatment, suggesting that submaximal balloon angioplasty might be in the sweet spot between mitigating early complications and securing long-term efficacy. These findings represent a significant advancement in the field, reinvigorating the goal of effective revascularization as a viable secondary prevention approach for intracranial atherosclerotic stenosis. However, several uncertainties still need to be addressed before the widespread implementation of angioplasty in clinical practice.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"56 4","pages":"e114-e118"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701462","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
Polygenic Risk Score for the Efficacy of Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the CHANCE Trial.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1161/STROKEAHA.124.049140
Xin Qiu, Yingyu Jiang, Hong-Qiu Gu, Yong Jiang, Xinying Huang, Xia Meng, Yongjun Wang, Zixiao Li
{"title":"Polygenic Risk Score for the Efficacy of Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the CHANCE Trial.","authors":"Xin Qiu, Yingyu Jiang, Hong-Qiu Gu, Yong Jiang, Xinying Huang, Xia Meng, Yongjun Wang, Zixiao Li","doi":"10.1161/STROKEAHA.124.049140","DOIUrl":"10.1161/STROKEAHA.124.049140","url":null,"abstract":"<p><strong>Background: </strong>Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).</p><p><strong>Methods: </strong>In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.</p><p><strong>Results: </strong>The elevated PRSs were associated with an increased risk of new stroke within 90 days (<i>P</i><sub>trend</sub>=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31-0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60-1.18]; <i>P</i><sub>interaction</sub>=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15-1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08-1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52-0.62), compared with 0.52 (95% CI, 0.48-0.55) for the ABCD-GENE score.</p><p><strong>Conclusions: </strong>Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT00979589.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"818-827"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573900","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
Innovative Real-World Data Use for Identifying Stroke Survivors and Access to Rehabilitation in Primary Care in Brazil.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-10 DOI: 10.1161/STROKEAHA.124.046946
M Julia Machline-Carrion, Alysson Nathan Girotto, Josué Nieri, Pedro Marton Pereira, Thais Cuperman-Poll, Peter Serafini
{"title":"Innovative Real-World Data Use for Identifying Stroke Survivors and Access to Rehabilitation in Primary Care in Brazil.","authors":"M Julia Machline-Carrion, Alysson Nathan Girotto, Josué Nieri, Pedro Marton Pereira, Thais Cuperman-Poll, Peter Serafini","doi":"10.1161/STROKEAHA.124.046946","DOIUrl":"10.1161/STROKEAHA.124.046946","url":null,"abstract":"<p><strong>Background: </strong>As the impact of stroke remains, primary healthcare will continue to be a critical platform managing the poststroke journey. We aimed to identify stroke survivors assisted by community health worker in Brazil and how they relate to the location of rehabilitation facilities locations.</p><p><strong>Methods: </strong>We developed a cross-sectional study using deidentified data from a real-world database generated by a free data collection app used by community health workers from May 2015 to January 2021 in Brazil to identify stroke survivors and to assess demographics and clinical characteristics. We used data from a public database, Cadastro Nacional de Estabelecimentos de Saúde, for identifying rehabilitation facilities. Locations were obtained by a geocoding application programming interface (Google Maps Platform), distances were measured in kilometers, and travel time in minutes.</p><p><strong>Results: </strong>Among 2 397 764 individuals assisted by community health workers, 21 785 were stroke survivors, representing a 0.9% prevalence. Among this subgroup, the majority were in the Northeast region (n=10 951; 50.3%) and 16 922 (77.7%) in urban areas. Most individuals (n=11 504; n=142; 52.8%) were women, the mean age was 66.5 (SD, 14.7), and 4313 reported physical disability. In total, 348 rehabilitation facilities were identified, mostly located in the Southeast region (40.8%). The mean distance from stroke survivor to facility was 79.13 km (SD, 97.73; median [1Q, 3Q], 47.64 km [12.19, 107.80 km]), and mean travel time was 81.18 minutes (SD, 85.85). The Southern region recorded the largest mean and median distance (mean 175.58 km; SD, 163.18; median [1Q, 3Q] 88.47 [59.38, 425.38]) to rehabilitation center and the longest mean travel time (144.48 minutes; SD, 112.57; median [1Q, 3Q] 92.34 [60.59, 305.12]).</p><p><strong>Conclusions: </strong>Despite the availability of rehabilitation centers in Brazil, geographic access as represented by the distances and travel times observed access is still suboptimal. As a means of improving the clinical pathway and resource allocation, the use of large real-world databases and adequate analysis may become a key component for real needs assessments.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"957-964"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587091","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
Speech Therapy Combined With Cerebrolysin in Enhancing Nonfluent Aphasia Recovery After Acute Ischemic Stroke: ESCAS Randomized Pilot Study.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI: 10.1161/STROKEAHA.124.049834
Volker Homberg, Dragoș Cătălin Jianu, Adina Stan, Ștefan Strilciuc, Vlad-Florin Chelaru, Michał Karliński, Michael Brainin, Wolf Dieter Heiss, Dafin F Muresanu, Pamela M Enderby
{"title":"Speech Therapy Combined With Cerebrolysin in Enhancing Nonfluent Aphasia Recovery After Acute Ischemic Stroke: ESCAS Randomized Pilot Study.","authors":"Volker Homberg, Dragoș Cătălin Jianu, Adina Stan, Ștefan Strilciuc, Vlad-Florin Chelaru, Michał Karliński, Michael Brainin, Wolf Dieter Heiss, Dafin F Muresanu, Pamela M Enderby","doi":"10.1161/STROKEAHA.124.049834","DOIUrl":"10.1161/STROKEAHA.124.049834","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Stroke-induced aphasia significantly impacts communication and quality of life. Despite the standard treatment being speech and language therapy, outcomes vary, highlighting the need for additional therapies. Cerebrolysin, a neuroprotective and neurotrophic agent, has shown potential in stroke management. This study addresses the notable gap in research about the combined use of Cerebrolysin and speech therapy, evaluating their synergistic potential in the treatment of aphasia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The ESCAS trial (The Efficacy and Safety of Cerebrolysin in the Treatment of Aphasia After Acute Ischemic Stroke), a prospective, randomized-controlled, double-blinded study was conducted in 2 Romanian stroke centers. Participants included those with left middle cerebral artery territory ischemic stroke and nonfluent aphasia, enrolled 3 to 5 days poststroke. Inclusion criteria were right-handedness and Romanian as the mother tongue. Participants received Cerebrolysin or a placebo combined with speech and language therapy in 10-day cycles over 3 intervals, and evaluations were done at baseline, 30, 60, and 90 days respectively. The main outcome measure was Western Aphasia Battery for language function. Changes at days 30, 60, and 90 compared with baseline were quantified, and the effect estimand used was the difference in means between groups. Secondary outcome measurements were the National Institutes of Health Stroke Scale for neurological deficit, the modified Rankin Scale for global disability, and the Barthel Index for activities of daily living.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Out of 132 enrolled patients, 123 were included in the intention-to-treat analysis, and 120 in the per-protocol analysis. Overall, both groups showed improvement at subsequent visits compared with the baseline for Western Aphasia Battery and the National Institutes of Health Stroke Scale. The Cerebrolysin group showed greater improvements in Western Aphasia Battery (visit 4 mean increase of 35.579±16.316 [95% CI, 31.289-39.869] points; &lt;i&gt;P&lt;/i&gt;&lt;0.001) compared with the placebo group (20.774±12.486 [95% CI, 17.603-23.945] points; &lt;i&gt;P&lt;/i&gt;&lt;0.001), a difference in means of 14.805 (95% CI, 9.521-20.089) points (&lt;i&gt;P&lt;/i&gt;&lt;0.001). The Cerebrolysin group also showed significant improvements (higher decreases) in National Institutes of Health Stroke Scale scores compared with the placebo group (2.085 [95% CI, 1.076-3.094] points; &lt;i&gt;P&lt;/i&gt;&lt;0.001). Safety analysis raised no concerns (number of patients with adverse events &lt;i&gt;P&lt;/i&gt;=0.105, number of adverse events per patient &lt;i&gt;P&lt;/i&gt;=0.134). Additionally, the Cerebrolysin group showed greater improvements in functional independence (Barthel Index) and a trend toward reduced disability (modified Rankin Scale) compared with the placebo group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Cerebrolysin combined with speech and language therapy offers promising potential for enhancing recovery in poststroke n","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"937-947"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433841","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
Atypical Nonfatal High-Altitude Cerebral Edema With Corpus Callosum Hemorrhage.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.1161/STROKEAHA.124.049977
Cesar Jara Silva, Solomon Nittala, Mitali Chansarkar, Brian Jose Villafuerte-Trisolini, Vivek Yedavalli
{"title":"Atypical Nonfatal High-Altitude Cerebral Edema With Corpus Callosum Hemorrhage.","authors":"Cesar Jara Silva, Solomon Nittala, Mitali Chansarkar, Brian Jose Villafuerte-Trisolini, Vivek Yedavalli","doi":"10.1161/STROKEAHA.124.049977","DOIUrl":"10.1161/STROKEAHA.124.049977","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"e112-e113"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542972","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
Spatial Transcriptomics and Proteomics Profiling After Ischemic Stroke Reperfusion: Insights Into Vascular Alterations. 缺血性中风再灌注后的空间转录组学和蛋白质组学分析:洞察血管变化。
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1161/STROKEAHA.124.048085
Line Mathilde Brostrup Hansen, Vibeke Secher Dam, Halvor Østerby Guldbrandsen, Christian Staehr, Tina Myhre Pedersen, Joanna Maria Kalucka, Hans Christian Beck, Dmitry D Postnov, Lin Lin, Vladimir V Matchkov
{"title":"Spatial Transcriptomics and Proteomics Profiling After Ischemic Stroke Reperfusion: Insights Into Vascular Alterations.","authors":"Line Mathilde Brostrup Hansen, Vibeke Secher Dam, Halvor Østerby Guldbrandsen, Christian Staehr, Tina Myhre Pedersen, Joanna Maria Kalucka, Hans Christian Beck, Dmitry D Postnov, Lin Lin, Vladimir V Matchkov","doi":"10.1161/STROKEAHA.124.048085","DOIUrl":"10.1161/STROKEAHA.124.048085","url":null,"abstract":"<p><strong>Background: </strong>More than half of patients with ischemic stroke experience futile reperfusion, increasing the risk of death and disabilities despite a successful recanalization. The reason behind this is debated, and we aim to investigate cerebrovascular changes toward a broader understanding of these conditions. We hypothesize that ischemic stroke reperfusion modifies the expression profile in the microvasculature in a spatial manner toward peri-infarct brain edema and circulatory failure.</p><p><strong>Methods: </strong>We investigated the early (24-hour) changes in spatial gene expression in the brain parenchymal endothelial cells and mural cells following ischemia stroke reperfusion in 13- to 14-week-old C57BL/6JRj male mice (n=5). Ischemia was induced by occlusion of the middle cerebral artery for 60 minutes, and Nissl staining was used to validate infarct size. Spatial transcriptomics complemented by bulk proteomics was conducted in the peri-infarct cortex region and validated with immunohistochemical semiquantification of proteins of interest. To avoid individual biological variations, changes in the peri-infarct cortex region were expressed relatively to the matching contralateral hemisphere region.</p><p><strong>Results: </strong>Ischemic stroke reperfusion impaired the blood-brain barrier integrity through junctional <i>Cldn5</i> (claudin-5) downregulation, changes of the actin cytoskeleton adhesion, and high expression of the proinflammatory <i>Il-6</i> (interleukin-6). Molecules important for extracellular Ca<sup>2+</sup> influx and intracellular Ca<sup>2+</sup> release, <i>Cacna1e</i> (R-type Ca<sup><i>2+</i></sup> <i>channels</i>), <i>Orai2</i>, <i>Ryr3</i>, <i>Itpr1</i>, and <i>Itpka</i> (inositol-trisphosphate 3-kinase A), were markedly reduced. Furthermore, reduced <i>Grm5</i> (glutamate receptor 5) associated with upregulated <i>Nfatc3</i> and <i>Stat3</i> implicates suppression of the contractile phenotype, suggesting reduced poststroke vascular resistance due to loss of mural cell tone. The complete spatial transcriptomics map over the ipsilateral and contralateral hemispheres is available online as a Web tool.</p><p><strong>Conclusions: </strong>Emphasizing the spatial molecular pattern behind blood-brain barrier disruption and loss of the vascular tone in the acute phase following ischemic stroke reperfusion suggests the gene expression contribution for a therapeutic target in ischemia-reperfusion abnormalities.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"1036-1047"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573953","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
Evaluation of Sex-Related Differences in Cerebrovascular Bypass Patency: Review of 357 Direct Cerebral Bypasses.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-02-27 DOI: 10.1161/STROKEAHA.124.049329
Laura Stone McGuire, Tatiana Abou-Mrad, Xinjian Du, Ali Alaraj, Sepideh Amin-Hanjani, Gursant Atwal, Fady T Charbel
{"title":"Evaluation of Sex-Related Differences in Cerebrovascular Bypass Patency: Review of 357 Direct Cerebral Bypasses.","authors":"Laura Stone McGuire, Tatiana Abou-Mrad, Xinjian Du, Ali Alaraj, Sepideh Amin-Hanjani, Gursant Atwal, Fady T Charbel","doi":"10.1161/STROKEAHA.124.049329","DOIUrl":"10.1161/STROKEAHA.124.049329","url":null,"abstract":"<p><strong>Background: </strong>Demographics and comorbid conditions play a role in vascular health, yet their specific impact on cerebrovascular bypass patency remains unclear.</p><p><strong>Methods: </strong>An institutional database of 357 patients with intracranial bypass procedures between August 2001 and May 2022 was retrospectively reviewed. Patients with bypass for all causes (eg, aneurysm, atherosclerotic disease, moyamoya disease) were included. Medical history, surgical technique, and flow-related measurements (intraoperatively and on quantitative magnetic resonance angiography at follow-up) were compared across biological sex and in relation to bypass patency. Bonferroni correction was applied to the initial analysis (<i>P</i>≤0.00167). The remaining analyses were considered exploratory. Propensity score-matched analysis matched cardiovascular risk factors and compared women and men in bypass patency.</p><p><strong>Results: </strong>Of 357 patients, 141 were men (39.5%) and 216 were women (60.5%) with average age of 49.0±16.7 years and an average follow-up of 1.97 years. Bypass patency at last follow-up was 84.4% (n=114) for men versus 69.2% (n=148) for women (<i>P</i>=0.001). Differences were seen in underlying diagnoses, with more aneurysm and moyamoya cases represented in female sex (<i>P</i><0.001); irrespective of diagnosis, lower patency rates were seen in women when considering bypass for aneurysm (<i>P</i>=0.032), moyamoya disease (<i>P</i>=0.035), and for atherosclerotic disease (<i>P</i>=0.159). Medical comorbidities were seen at higher rates in men, with comorbidity score of 2.7 versus 2.1 (<i>P</i><0.001). Cut flow was higher in men 59.2 versus 51.1 (<i>P</i>=0.028), with no differences in intraoperative bypass flow, cut flow index, or follow-up quantitative magnetic resonance angiography. After removing cases using interposition grafts, similar differences were redemonstrated. Propensity score-matched analysis found women have a 2.71 higher chance of bypass occlusion after adjusting for cut flow index (<i>P</i>=0.017 [95% CI, 1.19-6.18]).</p><p><strong>Conclusions: </strong>Biological sex appears to play a role in bypass patency, across diagnoses. Women were less likely to have patent bypasses at the last follow-up, despite having fewer medical comorbidities than men and despite having similar intraoperative and perioperative flows.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"828-837"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516791","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
Hematoma Expansion in Intracerebral Hemorrhage: Time Is the Enemy.
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1161/STROKEAHA.125.050756
Simon Fandler-Höfler, Santosh B Murthy
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引用次数: 0
Voxel-Wise Map of Intracerebral Hemorrhage Locations Associated With Worse Outcomes. 与较差预后相关的脑出血位置体素智图
IF 7.8 1区 医学
Stroke Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1161/STROKEAHA.124.048453
Gaby Abou Karam, Min-Chiun Chen, Dorin Zeevi, Bendix C Harms, Elisa Berson, Victor M Torres-Lopez, Cyprien A Rivier, Ajay Malhotra, Adnan I Qureshi, Guido J Falcone, Kevin N Sheth, Seyedmehdi Payabvash
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引用次数: 0
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