Stroke最新文献

{"title":"Digital Health in Low-Resource Settings: Comprehensive Challenges and Opportunities With a Focus on Stroke Care.","authors":"João Brainer Clares de Andrade, Thales Pardini Fagundes, Eric Katsuyama, Gisele Sampaio Silva","doi":"10.1161/STROKEAHA.125.050448","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.050448","url":null,"abstract":"<p><p>The global transition to digital health offers a critical opportunity to transform health care delivery, particularly in low- and middle-income countries. Stroke care exemplifies the need for timely, coordinated, and longitudinal management across health systems. Although substantial progress has been achieved, low- and middle-income countries continue to encounter persistent challenges, including infrastructural deficiencies, digital inequity, fragmented governance structures, and limitations within the health care workforce. Nonetheless, scalable digital health interventions, such as telestroke networks, mobile health platforms, artificial intelligence-supported diagnostics, and telerehabilitation programs, have demonstrated efficacy and impact across diverse contexts. The central challenge has, thus, shifted from technological development to the systemic integration of these solutions within existing health infrastructures. Crucially, low- and middle-income countries must not be perceived solely as passive recipients of technology but as active agents of innovation, developing efficient, adaptive, and culturally attuned models prioritizing community engagement and a holistic conception of health. To realize the transformative potential of digital health, it is imperative to invest not only in technological infrastructure but also in promoting digital literacy, establishing robust ethical and regulatory frameworks, fostering cross-sectoral partnerships, and creating inclusive innovation ecosystems. Only through such a comprehensive, human-centered approach can digital health effectively serve as a catalyst for more equitable, resilient, and sustainable health systems, particularly for populations residing in resource-constrained settings.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993567","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}

{"title":"Single-Cell Sequencing of Human Neural Organoids in a Model of Intracerebral Hemorrhage Reveals Temporally Dynamic Responses to Blood.","authors":"Carina Seah, Braxton R Schuldt, James M Vicari, Connie S Lebakken, William D Richards, Kaylie Greuel, Kailyn T Parham, Grace Rabinowitz, Christopher P Kellner","doi":"10.1161/STROKEAHA.125.051788","DOIUrl":"10.1161/STROKEAHA.125.051788","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage leads to significant morbidity and mortality due to primary mechanical and secondary neurotoxic injury to brain parenchyma. Timing of surgical evacuation to ensure optimal outcomes is controversial, with recent evidence suggesting early intervention improves functional outcome. Here, we characterize the impact of blood-induced secondary injury on diverse brain cell types in a scalable organoid model of intracerebral hemorrhage.</p><p><strong>Methods: </strong>Human neural organoids consisting of excitatory neurons, inhibitory neurons, neural progenitor cells, astrocytes, endothelial cells, and microglia were generated from induced pluripotent stem cell-derived cells and treated with 5% blood for either 6 or 24 hours. Organoids were dissociated and analyzed by single-cell RNA sequencing.</p><p><strong>Results: </strong>Single-cell sequencing of 96 725 cells across 18 organoids resolved intermediate progenitors, neural progenitor cells, microglia, inhibitory neurons, endothelial cells, excitatory neurons, and astrocytes. Twenty-four-hour exposure to blood induced cellular reactivity, whereas 6-hour exposure did not. Intermediate progenitors, endothelial cells, and astrocytes were the most reactive to blood and exhibited gene expression patterns corresponding to astrocyte reactivity, angiogenesis, and progenitor cell ischemic excitotoxicity. Drug repurposing analysis identified neurotransmitter-modulating, vasculature-remodeling, and protein synthesis pathways as potential therapeutic targets, mitigating blood-induced neurotoxicity.</p><p><strong>Conclusions: </strong>Blood exposure induces transcriptomic changes in a temporal and cell type-specific manner, particularly mediated by astrocyte reactivity, angiogenesis, and impairment of neurogenesis. Early and complete removal of blood after 6 hours of blood exposure mitigates secondary neurotoxicity seen in 24-hour exposure to blood. Transcriptomic signatures of blood-mediated neurotoxicity may potentially be reversed by antiadrenergic, dopamine agonist, and vasodilatory mechanisms.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993562","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}

{"title":"Risk of Stroke Recurrence Following Isolated Retinal Artery Occlusion Versus Minor Stroke or Transient Ischemic Attack.","authors":"Huanwen Chen, Marco Colasurdo, Julie Falardeau, Matthew K McIntyre, Ajay Malhotra, Thanh N Nguyen, James E Siegler, Dheeraj Gandhi","doi":"10.1161/STROKEAHA.125.052738","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052738","url":null,"abstract":"<p><strong>Background: </strong>Retinal artery occlusion (RAO) is a form of ischemic stroke per the American Heart Association, yet high-level evidence guiding management and prognostication is limited. The risk of future cerebral infarction following nonarteritic isolated RAO (iRAO; without concomitant cerebral infarction) is unclear. This study compares the risk of stroke recurrence following iRAO versus nondisabling ischemic cerebrovascular events (NICEs), including transient ischemic attacks and minor ischemic strokes.</p><p><strong>Methods: </strong>This was a retrospective cohort study using the 2016 to 2022 Nationwide Readmissions Database in the United States. Adults hospitalized primarily for RAO or NICE were included. Patients who were functionally dependent at discharge had moderate to severe stroke (National Institutes of Health Stroke Scale score >4), arteritis, or vasculitis, or RAO and concomitant cerebral infarction were excluded from the primary analysis. Two-to-one propensity score matching was performed to balance baseline characteristics between cohorts. The primary outcome was subsequent cerebral infarction within 300 days. Cox regression models and multivariable adjustments were used to estimate hazard ratios.</p><p><strong>Results: </strong>A total of 1 673 145 patients hospitalized for nondisabling stroke, transient ischemic attack, or RAO were identified; 17 388 (1.0%) had RAO, of whom 4507 (25.9%) had concomitant cerebral infarction and were excluded for primary analyses. After applying additional exclusion criteria and propensity score matching, 11 185 patients with nonarteritic iRAO and 22 757 patients with NICE remained. Patients with iRAO had a significantly lower risk of subsequent cerebral infarction (hazard ratio, 0.26 [95% CI, 0.20-0.35]; <i>P</i><0.001). Absolute cerebral infarction rates at 30, 90, and 180 days were lower in patients with iRAO versus patients with NICE (0.5% versus 2.3%, 0.8% versus 3.1%, and 1.2% versus 4.3%, respectively; all <i>P</i><0.001 for all).</p><p><strong>Conclusions: </strong>Nonarteritic iRAO events were associated with significantly lower risks of subsequent cerebral infarction compared with NICE. These findings suggest that iRAO events are not equivalent to ischemic cerebrovascular events in terms of risk of subsequent stroke. Further studies are needed to optimize secondary stroke prevention strategies tailored to nonarteritic iRAOs.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993514","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}

{"title":"SIN-1 Improves Cerebral Blood Flow and Reduces Deviation From Brain Homeostasis During Ischemia and Reperfusion in Rats.","authors":"Coline L Lemale, Lina M Serna-Higuita, Baptiste Balança, Sara Simula, Sebastian Major, Peter Martus, Ingemar Fredriksson, Jens P Dreier","doi":"10.1161/STROKEAHA.125.052917","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052917","url":null,"abstract":"<p><strong>Background: </strong>Overall, 75% of patients with acute stroke have elevated mean arterial pressure (MAP). In randomized stroke trials, the indirect NO donor glyceryl trinitrate lowered MAP but improved neither regional cerebral blood flow (rCBF) nor functional outcomes. One probable reason is that the microcirculation cannot bioactivate glyceryl trinitrate. In contrast, the direct NO donor 3-morpholinosydnonimine (SIN-1), not requiring bioactivation, should also release NO in small vessels, where it supports eNOS (endothelial NO synthase)-derived NO in maintaining rCBF in the hypotensive portion of Lassen autoregulatory curve. In a meta-analysis, SIN-1 reduced infarct volume in ischemia models, but the effects of SIN-1 on early pathophysiology are unknown.</p><p><strong>Methods: </strong>Here, we investigated SIN-1 during a 60-minute bilateral common carotid artery occlusion and reperfusion in forty-eight 12- to 14-week-old Wistar-Kyoto rat (WKY) controls and 48 stroke-prone spontaneously hypertensive rats. We calculated the difference between the median values of each variable in the last 5 minutes of bilateral common carotid artery occlusion and baseline and compared them between treatment (SIN-1/control) and strain (stroke-prone spontaneously hypertensive rat/WKY) using 2-way ANOVA. We proceeded in the same way regarding reperfusion.</p><p><strong>Results: </strong>Strain×intervention interaction was only found for MAP during bilateral common carotid artery occlusion. SIN-1 lowered MAP within stroke-prone spontaneously hypertensive rats (<i>P</i><0.001) and within WKY (<i>P</i><0.001), whereas MAP increased only in untreated stroke-prone spontaneously hypertensive rats versus untreated WKY (<i>P</i>=0.038). Across stroke-prone spontaneously hypertensive rat and WKY, SIN-1 increased rCBF (<i>P</i><0.001), increased spontaneous brain activity (<i>P</i>=0.002), lowered extracellular potassium concentration (<i>P</i>=0.009) and area under the curve of potassium (<i>P</i>=0.025), and reduced the direct current-amplitude (<i>P</i>=0.028) and cumulative direct current-shift duration (<i>P</i>=0.001), consistent with milder ischemia and less severe spreading depolarization load in SIN-1-treated animals. During reperfusion, SIN-1 lowered MAP (<i>P</i><0.001), decreased the no-reflow area (<i>P</i>=0.002), increased rCBF (<i>P</i><0.001), increased spontaneous brain activity (<i>P</i><0.001), and decreased extracellular potassium (<i>P</i>=0.008) and direct current potential (<i>P</i>=0.022) in both strains, consistent with less no-reflow and better recovery in SIN-1-treated animals.</p><p><strong>Conclusions: </strong>SIN-1 emerges as a promising antihypertensive in acute stroke as it paradoxically increases rCBF in ischemic tissue and reduces no-reflow.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993554","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}

{"title":"Fingolimod as a Potential Cerebroprotectant Results From the Stroke Preclinical Assessment Network.","authors":"Ligia S B Boisserand, Alison L Herman, Basavaraju G Sanganahalli, Jelena Mihailovic, Hannah E Beatty, Conor W Johnson, Sebastian Diaz, Jonathan H DeLong, Sofia Velazquez, Jaime Grutzendler, Charles Dela Cruz, Jiangbing Zhou, Kevin N Sheth, Charles Matouk, Shenqi Zhan, Andreia Morais, Takahiko Imai, Anjali Chauhan, Rakesh B Patel, Mariia Kumskova, Yanrong Shi, Brooklyn D Avery, Jessica Lamb, Karisma A Nagarkatti, Mohammad B Khan, Pradip K Kamat, Krishnan M Dhandapani, Louise D McCullough, Jaroslaw Aronowski, David Hess, Raymond C Koehler, Patrick Lyden, Enrique C Leira, Anil K Chauhan, Cenk Ayata, Mu-Hsun Chen, Marcio A Diniz, Fahmeed Hyder, Lauren H Sansing","doi":"10.1161/STROKEAHA.125.050903","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.050903","url":null,"abstract":"<p><strong>Background: </strong>Fingolimod is an immunomodulatory drug that has shown promising effects in stroke treatment, including improvements in neurofunctional recovery and a reduction in infarct size. Fingolimod modulates the sphingosine-1-phosphate receptors, which leads to the internalization of sphingosine-1-phosphate receptors on T and B lymphocytes, thereby preventing their egress from secondary lymphoid organs. Here, we report a secondary analysis from the Stroke Preclinical Assessment Network trial. We assessed the effects of fingolimod versus vehicle on stroke outcomes to better evaluate its therapeutic potential.</p><p><strong>Methods: </strong>The animal population (n=409) comprised male and female animals treated with fingolimod or vehicle. We used 4 clinically relevant models: young healthy mice (10-12 weeks-old), aging mice (16±1 month-old), obesity induced-hyperglycemic mice fed with a high-fat diet for 12 weeks (16 weeks-old), and spontaneously hypertensive rats (16±1 weeks-old). Stroke was induced by the middle cerebral artery occlusion for 1 hour, followed by reperfusion. Animals received a total of 6 intraperitoneal injections of 0.5 mg/kg twice daily of fingolimod or vehicle. Functional outcomes in the corner test and foot-faults test were measured at days 7 and 28. Lesion size and brain morphometry were evaluated at days 2 and 30 by magnetic resonance imaging.</p><p><strong>Results: </strong>Overall, fingolimod did not improve morphological and functional outcomes. However, fingolimod effects varied depending on sex or the comorbidity model. Fingolimod promoted a better outcome in the corner test in aging females. In contrast, it favored a worse outcome in obesity-induced hyperglycemic mice at day 7. Despite having no effect on survival rates or lesion size, fingolimod attenuated the midline retraction at day 30 in aging males, consistent with less atrophy.</p><p><strong>Conclusions: </strong>Although fingolimod did not significantly benefit the overall primary functional outcome, its effects varied with sex and comorbidity models, underscoring how the therapeutic potential of a particular drug can differ in a heterogeneous population.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969730","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}

{"title":"Time to Acute Treatment in Intracerebral Hemorrhage Lags Significantly Behind Ischemic Stroke: A Multicenter, Observational Retrospective Study.","authors":"Kara R Melmed, Abhijit V Lele, Maranatha Ayodele, Joshua N Goldstein, Aaron LacKamp, Keith E Dombrowski, Ayham Alkhachroum, Shraddha Mainali, Adam de Havenon, Prashanth Krishnamohan, Thanujaa Subramaniam, Christoph Stretz, Wen-Yu Lee, Lindsey Kuohn, Christine T Fong, Sean McDougall, Robert Kim, Shlee S Song, Alexis Campbell, Aneesh B Singhal, Margaret Houghton, Shrinit Babel, Sebastian Koch, Jude Hassan Charles, Kristine H O'Phelan, Stacie Stevens, Vivian Li, Alison Champagne, Joseph Madour, Kevin N Sheth, Chitra Venkatasubramanian, Shadi Yaghi, Stephan A Mayer, Iván Díaz, Jennifer A Frontera","doi":"10.1161/STROKEAHA.125.051422","DOIUrl":"10.1161/STROKEAHA.125.051422","url":null,"abstract":"<p><strong>Background: </strong>Time-to-treatment goals for acute ischemic stroke (AIS) have substantially improved outcomes, yet similar metrics have not been studied in patients with intracerebral hemorrhage (ICH), where mortality rates are much higher.</p><p><strong>Methods: </strong>Multicenter, observational retrospective study of patients with ICH and AIS between January 1, 2017, and December 31, 2022, in 11 comprehensive stroke centers across the United States participating in Get With The Guidelines. We included patients with ICH who received antihypertensive therapy and anticoagulation reversal, and patients with AIS requiring intravenous thrombolytic and mechanical thrombectomy. The coprimary outcomes included (1) time-to-treatment and (2) the percentage of patients meeting current national time interval goals. Multivariable logistic regression models controlling for age, sex, race and ethnicity, time to arrival, National Institutes of Health Stroke Scale score, arrival systolic blood pressure, and admission international normalized ratio were constructed to assess the likelihood of patients with ICH being treated within goal compared with patients with AIS. Multivariable logistic regression models were constructed to assess the impact of treatment time on mortality or discharge disposition in patients with ICH.</p><p><strong>Results: </strong>A total of 28 180 patients were identified, of which 7003 patients were included: n=1972 ICH (mean age, 67; 43% female) and n=5031 AIS (mean age, 69; 49% female). The median door-to-first medication was 52 (28-157) minutes for patients with ICH and 42 (30-63) minutes for patients with AIS (<i>P</i><0.001). Fifty-three percent of patients with ICH received antihypertensive medications in ≤60 minutes from arrival compared with 74% of patients with AIS who received intravenous thrombolytic ≤60 minutes (<i>P</i><0.001). Thirty-seven percent of patients with ICH received anticoagulation reversal ≤90 minutes from arrival compared with 47% of patients with AIS with door-to-puncture times ≤90 minutes (<i>P</i><0.001). The adjusted odds of timely treatment in patients with ICH compared with patients with AIS are less than three-fourths (adjusted odds ratio, 0.74 [95% CI, 0.61-0.89]; <i>P</i><0.01). Patients with ICH who received antihypertensive treatment ≤60 minutes from arrival had a higher likelihood of discharge to home or acute rehab unit (adjusted odds ratio, 7.48 [95% CI, 1.99-28.09]; <i>P</i><0.01) compared with those treated in >60 minutes.</p><p><strong>Conclusions: </strong>Time-to-treatment for patients with ICH is significantly longer than for patients with AIS. Faster antihypertensive treatment times are associated with better discharge outcomes in patients with ICH.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969776","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}

{"title":"Venous Architecture Predicts Hemorrhage Risk in Sporadic CCM With DVA.","authors":"Yang Liu, Zheng Wen, Jing Yuan, Li Ma, Chunxue Wu, Jun Wu, Qingyuan Liu, Shuo Zhang, Shuo Wang","doi":"10.1161/STROKEAHA.125.052339","DOIUrl":"10.1161/STROKEAHA.125.052339","url":null,"abstract":"<p><strong>Background: </strong>To prospectively validate an imaging-based classification system for cerebral cavernous malformation (CCM) associated with developmental venous anomaly (DVA) in a multicenter cohort, and to evaluate the association between DVA subtypes and hemorrhage risk.</p><p><strong>Methods: </strong>This prospective multicenter cohort study was conducted as part of the Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy (CRESS) study at 2 tertiary neurosurgical centers in China. Patients with sporadic CCM and coexisting DVA were consecutively enrolled and prospectively followed for data collection between September 2019 and March 2024. Eligible patients had a single sporadic CCM with a coexisting DVA, confirmed by contrast-enhanced magnetic resonance imaging or susceptibility-weighted imaging, and provided written informed consent for scheduled follow-up. Patients were classified into 3 subtypes (Groups A, B, and C) based on DVA morphology and its anatomic relationship with the CCM by 2 independent neuroradiologists blinded to outcomes. Clinical, demographic, and imaging data were collected, and patients were followed at scheduled intervals. The primary outcome was symptomatic hemorrhage. Outcomes were assessed throughout the follow-up period from enrollment until the first occurrence of symptomatic hemorrhage or censoring. Kaplan-Meier survival analysis and multivariable Cox regression were used to assess hemorrhage risk across subtypes.</p><p><strong>Results: </strong>Of the 237 patients, 37.6% were classified as Group A, 13.5% as Group B, and 48.9% as Group C. Over a median follow-up of 51.4 months, 75 (31.5%) patients experienced hemorrhagic events. Group C showed a markedly higher annual hemorrhage incidence (17.2 per 100 patient-years) compared with Group A (4.1 per 100 patient-years) and Group B (2.2 per 100 patient-years). Multivariable analysis confirmed that Group C was independently associated with increased hemorrhage risk compared with Group A (adjusted hazard ratio, 4.51 [95% CI, 2.42-8.40]). Other significant predictors included infratentorial location (hazard ratio, 2.67 [95% CI, 1.61-4.49]), history of previous hemorrhage (hazard ratio, 2.04 [95% CI, 1.24-3.35]), and Zabramski type I lesions (hazard ratio, 1.94 [95% CI, 1.02-3.72]).</p><p><strong>Conclusions: </strong>CCM located at the distal branches of DVA with radially converging veins (Group C) carries a significantly higher risk of symptomatic hemorrhage. This imaging-based classification offers a practical framework for risk stratification and may inform individualized surveillance strategies.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04076449.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969837","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}

{"title":"MFN2 and BAG6 Synergistically Protect Against Cerebral Reperfusion Injury by Regulating ROS Levels and Autophagic Flux.","authors":"Dongting Lu, Yukun Yang, Guodong Huang, Qinlian Ye, Xingyun Quan, Britta Kaltwasser, Yanfen Liu, Dirk M Hermann, Ulf Brockmeier, Ya-Chao Wang","doi":"10.1161/STROKEAHA.125.052689","DOIUrl":"10.1161/STROKEAHA.125.052689","url":null,"abstract":"<p><strong>Background: </strong>MFN2 (mitofusin-2), a transmembrane dynamin-like protein located on the outer mitochondrial membrane, plays a key role in regulating mitochondrial fusion and autophagy. In vitro studies suggested that MFN2 may exert neuroprotective effects postischemia. In gain-of-function and loss-of-function experiments, we investigated MFN2'·s roles in regulating neuronal ischemia/reperfusion injury in vivo and in vitro.</p><p><strong>Methods: </strong>MFN2 was knocked down by neuron-specific conditional knockout or siRNA-mediated knockdown and overexpressed by adeno-associated viral vectors or plasmid vectors in C57BL/6 mice of both sexes (10-12 weeks) exposed to middle cerebral artery occlusion and SY5Y cells exposed to oxygen-glucose deprivation/reoxygenation. Neurological deficits were examined using a 48-point score and rotarod tests. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining. A RealTime Apoptosis and Necrosis Assay was used to measure apoptotic and necrotic cell death. Reactive oxygen species (ROS) formation and autophagic flux were analyzed by functional assays. Protein expression and interaction were evaluated using Western blots, immunoaffinity chromatography, mass spectrometry, and immunoprecipitation analysis. To assess the role of MFN2's interaction partner BAG6, BAG6 was overexpressed in middle cerebral artery occlusion mice and overexpressed or knocked down in SY5Y cells.</p><p><strong>Results: </strong>Neuron-specific MFN2 deletion exacerbated cerebral ischemia/reperfusion injury, while MFN2 overexpression reduced it. MFN2 deficiency elevated mitochondrial ROS levels and inhibited autophagy, whereas MFN2 overexpression decreased ROS levels. In immunoprecipitation studies, we found a direct interaction between MFN2 and BAG6. Of note, BAG6 overexpression mimicked the effect of MFN2 overexpression on cerebral ischemia/reperfusion injury. Combined MFN2 and BAG6 overexpression synergistically reduced ischemia/reperfusion injury by drastically decreasing cerebral ROS levels, stabilizing mitochondrial function, and modulating autophagy.</p><p><strong>Conclusions: </strong>Our study suggests that MFN2 enhances stroke outcome through 2 pathways: by decreasing ROS levels and modulating autophagy via interaction with BAG6. BAG6 potentiates the ROS-lowering, cytoprotective MFN2 actions. The MFN2-BAG6 axis represents a promising target for stroke therapy.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969806","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}

{"title":"Apixaban and Recurrent Stroke Risk With Left Ventricular Dysfunction: A Secondary Analysis of the ARCADIA Trial.","authors":"Richa Sharma, Dinesh Jillella, Cenai Zhang, Mitchell S V Elkind, Hooman Kamel, Marco R Di Tullio, Richard A Kronmal, Balaji Krishnaiah, Shadi Yaghi, W T Longstreth, David Tirschwell, Alexander Merkler, Fadi Nahab","doi":"10.1161/STROKEAHA.125.052724","DOIUrl":"10.1161/STROKEAHA.125.052724","url":null,"abstract":"<p><strong>Background: </strong>Major uncertainty remains about the relationship between left ventricular (LV) systolic dysfunction, recurrent stroke, and the optimal antithrombotic therapy for secondary stroke prevention in patients with recent stroke and LV systolic dysfunction.</p><p><strong>Methods: </strong>We performed a post hoc analysis of data from the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke), a randomized trial comparing apixaban versus aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. Echocardiograms were sent from 185 enrolling sites in the United States and Canada for central review at the trial echocardiography laboratory. We defined LV systolic dysfunction as LV fractional shortening <25%, LV ejection fraction <50%, or any LV wall motion abnormality. The primary outcome of interest was recurrent ischemic stroke. First, we built Cox proportional hazard models to evaluate the association between LV systolic dysfunction and recurrent ischemic stroke risk adjusted for imbalanced covariates. Next, we used Cox proportional hazard models and interaction terms to compare the effect of apixaban versus aspirin on the outcome of interest in patients with and without LV systolic dysfunction.</p><p><strong>Results: </strong>Among 964 patients with complete echocardiographic data of the 1015 patients enrolled in the trial, 165 (17.1%) had LV systolic dysfunction (mean age, 67 years; 43% female; mean follow-up, 1.7 years), and 799 (82.9%) had no LV systolic dysfunction (mean age, 68 years; 56% female; mean follow-up, 1.5 years). Recurrent ischemic stroke occurred more frequently in patients with LV systolic dysfunction (n=15, 9.1%) compared with those without LV systolic dysfunction (n=50, 6.3%), but LV systolic dysfunction was not significantly associated with recurrent stroke after adjustment for imbalanced covariates (hazard ratio, 1.3 [95% CI, 0.7-2.4]). Compared with aspirin, apixaban was associated with a significantly reduced risk of recurrent ischemic stroke in patients with LV systolic dysfunction (hazard ratio, 0.24 [95% CI, 0.07-0.87]) but not in those without LV systolic dysfunction (hazard ratio, 1.13 [95% CI, 0.65-1.96]; <i>P</i>_interaction=0.028).</p><p><strong>Conclusions: </strong>In a secondary analysis of the ARCADIA trial data, apixaban was associated with a significantly lower risk of recurrent ischemic stroke than aspirin in patients with LV systolic dysfunction.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969651","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}

{"title":"Hospital Implementation of Endovascular Thrombectomy and Health Equity in Acute Stroke Outcomes.","authors":"Jay B Lusk, Bo Liu, Emily O'Brien, David Hasan, Gregg C Fonarow, Kevin Sheth, Lee H Schwamm, Ying Xian, Gregory W Albers, Jeffrey L Saver, Fan Li, Brian Mac Grory","doi":"10.1161/STROKEAHA.125.051312","DOIUrl":"10.1161/STROKEAHA.125.051312","url":null,"abstract":"<p><strong>Background: </strong>The introduction of novel therapeutics into clinical practice could impact equity in health outcomes.</p><p><strong>Methods: </strong>This was a retrospective, observational cohort study based on the Get With The Guidelines-Stroke program of the American Heart Association. Two epochs were considered: January 2010 to December 2014 and January 2016 to December 2019. The primary exposure was the availability of endovascular thrombectomy (EVT) at the hospital level defined by the degree of implementation of EVT (>10% change from pre-2015 to post-2015) after balancing key patient and hospital characteristics with overlap weighting. The coprimary end points were (1) the difference in in-hospital mortality for patients from counties with median income >$60 000 versus <$60 000 and (2) the difference in in-hospital mortality between Black and White patients. Secondary end points were differences in in-hospital mortality by sex, insurance status, county-level poverty, and county-level educational attainment. Exploratory end points were differences in ambulatory status at hospital discharge and a composite of in-hospital mortality/discharge to hospice across the above categories.</p><p><strong>Results: </strong>Of 173 049 patients (median age, 75 years; 53.9% female) potentially eligible for EVT, 39 196 (22.7%) received EVT (7572 [10.0% of potentially eligible patients] between 2010 and 2014 and 31 624 [32.6% of potentially eligible patients] between 2016 and 2019). From 2010 to 2014, 1565 (20.7%) of patients and from 2016 to 2019, 5158 (16.3%) who received EVT died in hospital. Implementation of EVT was associated with decreased disparities in mortality rates for patients from counties with median inflation-adjusted income >$60 000 versus <$60 000 (absolute risk difference, 3.9% [95% CI, 0.53%-7.3%]). Implementation of EVT was not associated with changes in differences in in-hospital mortality by race, sex, county poverty rates, county educational attainment, or insurance status.</p><p><strong>Conclusions: </strong>Among patients with acute ischemic stroke who were potentially eligible for EVT, the implementation of EVT on a hospital level did not worsen health equity in any dimension (race/ethnicity, sex, or insurance status) and was associated with improvements in socioeconomic equity in acute ischemic stroke mortality.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969686","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}