Stroke最新文献

{"title":"Topographic Localization of Chronic Cerebellar Ischemic Lesions: Implications for Underlying Cause.","authors":"Markus Kneihsl, Arsany Hakim, Martina B Goeldlin, Mattia Branca, Sabine Fenzl, Stefanie Abend, Thomas Gattringer, Christian Enzinger, Jesse Dawson, Benno Gesierich, Anna Kopczak, Remco J Hack, Minne N Cerfontaine, Julie W Rutten, Saskia A J Lesnik Oberstein, Marco Pasi, Urs Fischer, Marco Duering, Thomas R Meinel","doi":"10.1161/STROKEAHA.124.049337","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049337","url":null,"abstract":"<p><strong>Background: </strong>Chronic cerebellar lesions of presumed ischemic origin are frequently found in patients with ischemic stroke and as incidental findings. However, the differentiation of embolic lesions from lesions caused by cerebral small vessel disease (SVD) is unclear. We aimed to investigate whether the location of chronic cerebellar ischemic lesions (deep versus cortical) indicates the underlying cause (embolic versus SVD).</p><p><strong>Methods: </strong>This study was a post hoc data analysis from the multinational ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Patients With Postischemic Stroke With Atrial Fibrillation), which included patients with acute ischemic stroke and atrial fibrillation cohort between 2017 and 2022. For comparison, data from 2 cohorts (DiViNAS [Disease Variability in NOTCH3-Associated SVD] and VASCAMY [Vascular and Amyloid Predictors of Neurodegeneration and Cognitive Decline in Nondemented Subjects]) consisting of participants with hereditary cerebral SVD (ie, Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) were analyzed (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy cohort). Brain magnetic resonance imaging scans were evaluated for presence and location of chronic cerebellar ischemic lesions. The association between these lesions and the severity of supratentorial SVD was analyzed using univariable and multivariable models, adjusting for key covariables.</p><p><strong>Results: </strong>In the atrial fibrillation cohort (N=790), 278 (35%) patients had chronic cerebellar ischemic lesions (cortical: n=242; deep: n=36). In multivariable analyses, features of cerebral SVD were associated with deep cerebellar ischemic lesions (summary SVD score; odds ratio per point, 2.5 [95% CI, 1.5-3.5]; <i>P</i><0.001), while there was no association of SVD markers and cortical cerebellar ischemic lesions (summary SVD score; odds ratio per point, 1.1 [95% CI, 0.9-1.3]; <i>P</i>=0.107). In the Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy cohort (N=257), chronic cerebellar ischemic lesions (n=108 [42%]) were almost exclusively identified in deep cerebellar regions (n=101, 94%).</p><p><strong>Conclusions: </strong>Chronic cerebellar ischemic lesions in deep but not cortical regions were associated with supratentorial cerebral SVD. Therefore, cerebral SVD is likely the primary cause of chronic ischemic lesions in deep cerebellar regions, while cortical cerebellar lesions are more likely attributable to embolic etiologies.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03148457.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773105","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":"Assessing the Impact of the COVID-19 Pandemic on Childhood Arterial Ischemic Stroke: An Unanticipated Natural Experiment.","authors":"Heather J Fullerton, Nancy K Hills, Max Wintermark, Nomazulu Dlamini, Christine K Fox, Dana D Cummings, Timothy J Bernard, Lauren A Beslow, Lisa R Sun, Charles Grose, Phillp J Norris, Clara Di Germanio","doi":"10.1161/STROKEAHA.124.049909","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049909","url":null,"abstract":"<p><strong>Background: </strong>The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact.</p><p><strong>Methods: </strong>Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3-6 months). We assessed clinical infection via parental interview.</p><p><strong>Results: </strong>The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%; <i>P</i>=0.02) and more focal cerebral arteriopathy (20% versus 11%; <i>P</i>=0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children (<i>P</i>=0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9-95.3) in the positive cases and 18.8 (12.0-101) in the positive well children (<i>P</i>=0.33).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765050","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":"Small Extracellular Vesicles From Hypoxia-Neuron Maintain Blood-Brain Barrier Integrity.","authors":"Wei Chen, Yousheng Wu, Ying Liang, Xuanlin Su, Man Ke, Die Deng, Jiankun Zang, Jielin Zhu, Hongcheng Mai, Anding Xu, Dan Lu","doi":"10.1161/STROKEAHA.124.048446","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.048446","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke disrupts communication between neurons and blood vessels in penumbral areas. How neurons and blood vessels cooperate to achieve blood-brain barrier repair remains unclear. Here, we reveal crosstalk between ischemic penumbral neurons and endothelial cells (ECs) mediated by circular RNA originating from oxoglutarate dehydrogenase (CircOGDH).</p><p><strong>Methods: </strong>We analyzed clinical data from patients with acute ischemic stroke to explore the relationship between CircOGDH levels and hemorrhagic transformation events. In addition, a middle cerebral artery occlusion and reperfusion mouse model with neuronal CircOGDH suppression was used to assess endothelial permeability. ECs with increased CircOGDH expression were analyzed for changes in COL4A4 (collagen type IV alpha 4) levels, and in vitro coculture experiments were conducted to examine small extracellular vesicle-mediated CircOGDH transfer between neurons and ECs.</p><p><strong>Results: </strong>Clinical data indicated that reduced CircOGDH levels were correlated with increased hemorrhagic transformation in patients with acute ischemic stroke. In the middle cerebral artery occlusion and reperfusion model, neuronal CircOGDH suppression impaired the restoration of endothelial permeability. ECs with increased CircOGDH expression exhibited higher COL4A4 levels, which helped maintain vascular stability. In vitro, hypoxic neurons transferred CircOGDH to ECs via small extracellular vesicles, leading to elevated COL4A4 expression and enhanced endothelial integrity.</p><p><strong>Conclusions: </strong>Our findings highlight the significance of CircOGDH in neuron-EC crosstalk via small extracellular vesicles in the ischemic penumbra, emphasizing the need for balanced intervention strategies in acute ischemic stroke management.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765089","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":"Comparison of the Novel Thrombolytic Constitutively Active ADAMTS13 With Clinical Thrombolytics in a Murine Stroke Model.","authors":"Lucy Roberts, Graham Coutts, Ben Dickie, Craig J Smith, Kieron South, Stuart M Allan","doi":"10.1161/STROKEAHA.125.050848","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.050848","url":null,"abstract":"<p><strong>Background: </strong>rtPA (recombinant tissue-type plasminogen activator) and its variant, TNK (tenecteplase), are the currently approved thrombolytic drugs for the treatment of acute ischemic stroke, but they are ineffective in a proportion of patients due to rtPA resistance of platelet-rich thrombi. A novel thrombolytic, constitutively active caADAMTS13 (constitutively active a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) has been shown to improve experimental stroke outcomes where platelet-rich thrombi are present but have not been directly compared with rtPA or TNK.</p><p><strong>Methods: </strong>We conducted a direct comparison of caADAMTS13 versus rtPA versus TNK versus vehicle control in the ferric chloride-mediated distal middle cerebral artery occlusion model in mice, which features platelet and VWF (von Willebrand Factor)-rich thrombi that reproduce rtPA-resistant occlusion. Treatments were administered intravenously 1 hour after ferric chloride application by bolus injection or bolus followed by infusion, as translationally applicable. Laser speckle contrast imaging measured early reperfusion over the hour following treatment, and magnetic resonance imaging measured cerebral blood flow and lesion volume at 24 hours.</p><p><strong>Results: </strong>Reperfusion 1 hour after treatment was greatest in caADAMTS13-treated animals. Later cerebral blood flow, 24 hours post-treatment, within the stroke-affected hypoperfused area was higher in caADAMTS13 and rtPA but not TNK-treated mice. Functionally, this led to the absence of an initial behavioral deficit in caADAMTS13-treated mice, alongside a smaller lesion volume at 24 hours and reduced extent of bleeding.</p><p><strong>Conclusions: </strong>These findings demonstrate an overall suggestion that caADAMTS13 has improved thrombolytic efficacy, compared with current stroke treatments, against platelet-rich thrombi, for which there is currently an unmet clinical need.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765077","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":"Mediolateral Diameter of the Falcine Sinus as a Predictor of Clinical Outcomes in Fetal Vein of Galen Malformations.","authors":"Patrisha C Lazatin, Emma N Puglisi, Julie Meadows, Kittiphop Somboonnithiphol, Alfred P See, Darren B Orbach","doi":"10.1161/STROKEAHA.125.050694","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.050694","url":null,"abstract":"<p><strong>Background: </strong>The mediolateral diameter of the falcine sinus (FS) on fetal magnetic resonance imaging is a robust predictor of aggressive neonatal presentation requiring early treatment in vein of Galen malformation. Given the need for better overall prognostication for fetal vein of Galen malformation, we aimed to assess whether FS provides a more comprehensive prediction of outcomes.</p><p><strong>Methods: </strong>Patients were identified retrospectively from a single referral center cerebrovascular database. Overall, 59 patients (55% male and 45% female) diagnosed with vein of Galen malformation via fetal magnetic resonance imaging from 2002 to 2024 were included. Median gestational age was 34 weeks (interquartile range, 31.7-36.6 weeks). FS was measured by 2 pediatric neurointerventionalists, with interrater reliability measured via intraclass coefficient. Clinical outcomes were measured at 1, 6, and 12 months after discharge. Radiological outcomes were measured at birth, discharge, and 3 to 9 months after discharge. FS was correlated with clinical outcomes using logistic regression, with the predicted risk of the outcome per unit FS measurement calculated through marginal analysis. Regressions were adjusted for treatment effect with inverse probability weighting.</p><p><strong>Results: </strong>The median FS was 6 mm (interquartile range, 4-9 mm; intraclass coefficient, 0.90). FS predicted mortality (<i>P</i>=8.04×10^-9), right ventricular systolic dysfunction at discharge (<i>P</i>=0.02), brain parenchymal abnormalities at birth (<i>P</i>=0.02) and discharge (<i>P</i>=0.02), ventriculomegaly at birth (<i>P</i>=0.03), and developmental delay at 1 month (<i>P</i>=0.001), 6 months (<i>P</i>=0.001), and 12 months (<i>P</i>=0.002). Inverse probability weighting showed that the treatment effect of embolization was negligible for most outcomes. Marginal analysis revealed that risk for mortality, brain parenchymal abnormalities, ventriculomegaly, and developmental delay increased significantly at FS=5 mm and FS=9 mm.</p><p><strong>Conclusions: </strong>A wide FS is robustly predictive of a high risk for mortality, cardiac dysfunction, brain parenchymal abnormalities at birth, and short- and intermediate-term neurodevelopmental delay. This finding can facilitate discussions between clinicians and families and corroborates that FS is useful for identifying cohorts that may benefit from fetal intervention.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765078","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":"Diffusion Imaging Protocol Heterogeneity Biases Ischemic Core Volume, Location, and Clinical Associations in Acute Stroke.","authors":"Jonathan Rafael-Patiño, Elda Fischi-Gomez, Antoine Madrona, Veronica Ravano, Bénédicte Maréchal, Tobias Kober, Silvia Pistocchi, Alexander Salerno, Guillaume Saliou, Patrik Michel, Roland Wiest, Richard McKinley, Jonas Richiardi","doi":"10.1161/STROKEAHA.124.047317","DOIUrl":"10.1161/STROKEAHA.124.047317","url":null,"abstract":"<p><strong>Background: </strong>Diffusion-weighted magnetic resonance imaging is essential for diagnosing ischemic stroke and identifying targets for emergency revascularization. Apparent diffusion coefficient (ADC) maps derived from diffusion-weighted magnetic resonance imaging are commonly used to locate the infarct core, but they are not strictly quantitative and can vary across platforms and sites due to technical factors. This retrospective study was conducted to examine how differences in ADC map generation, resulting from varied protocols across platforms and sites, affect the determination of infarct core size, location, and related clinical outcomes in acute stroke.</p><p><strong>Methods: </strong>In this retrospective study, 726 patients with acute anterior circulation stroke from a cohort of 1210 unique visits to the Lausanne University Hospital between May 2018 and January 2021 were selected, excluding patients with poor quality imaging or no magnetic resonance imaging or clinical information available. Diffusion-weighted magnetic resonance imaging data were used to generate ADC maps as they would appear from different protocols: 2 simulated with low- and medium-angular resolution (4 and 12 diffusion gradient directions) and 1 with high-angular resolution (20 directions). Using DEFUSE criteria and image postprocessing, ischemic cores were localized; core volume, location, and associations to the National Institutes of Health Stroke Scale and modified Rankin Scale scores were compared between the 2 imaging sequences.</p><p><strong>Results: </strong>Significant differences were observed in the ADC distribution within white matter, particularly in the kurtosis and skewness, with the segmented infarct core volume being higher in protocols with reduced angular resolution compared with the 20-directions data (7.63 mL versus 3.78 mL). The volumetric differences persisted after correcting for age, sex, and type of intervention. Infarcted voxel's locations varied significantly between the 2 protocols. This variability affected associations between infarct core volume and clinical scores, with lower associations observed for 4-direction data compared with 20-direction data for the National Institutes of Health Stroke Scale at admission and after 24 hours, and modified Rankin Scale after 3 months, further confirmed by multivariate regression.</p><p><strong>Conclusions: </strong>Imaging protocol heterogeneity leads to significant changes in the ADC distribution, ischemic core location, size, and association with clinical scores. Work is needed in standardizing imaging protocols to improve the reliability of ADC as an imaging biomarker in stroke management protocols to improve the reliability of ADC as an imaging biomarker in stroke management.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"56 4","pages":"915-925"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Intermittent Hypoxia in People Living With Chronic Stroke: A Case Series.","authors":"Gregory E P Pearcey, Alexander J Barry, Milap S Sandhu, Timothy J Carroll, Elliot J Roth, W Zev Rymer","doi":"10.1161/STROKEAHA.124.046620","DOIUrl":"10.1161/STROKEAHA.124.046620","url":null,"abstract":"<p><strong>Background: </strong>Acute intermittent hypoxia (AIH) is a novel therapeutic intervention that facilitates recovery of function, but the tolerability and effectiveness have not been tested in people living with chronic stroke. The purpose here was to examine whether AIH is tolerable and effective in this population.</p><p><strong>Methods: </strong>Ten participants with a unilateral, hemispheric stroke were assessed before and after 4 sessions of AIH separated by ≥48 hours in a case series at Shirley Ryan AbilityLab (Chicago). Physician-assessed signs and symptoms (assessed via: repeated symptom reviews, National Institutes of Health Stroke Scale, cranial nerve assessment, a muscle strength test, the Brunnstrom scale, sensory changes, reflexes, assessment of heart and lung status, Fugl-Meyer test, Chedoke-McMaster Stroke Assessment, Modified Ashworth Scale for Spasticity, and Delis Kaplan Executive Function System Color-Word Interference Test) and bilateral upper limb strength (grip and elbow flexion) were assessed before, ≈15 to 30 minutes, and ≈60 minutes after the intervention.</p><p><strong>Results: </strong>AIH was well-tolerated and there were no adverse events observed. After AIH, grip strength (12.91% and 16.53% improvement at 30 and 60 minutes post-AIH, respectively) and elbow flexion force (5.87% and 7.01% improvement at 30 and 60 minutes post-AIH, respectively) improved in the more-affected limb.</p><p><strong>Conclusions: </strong>AIH is potentially safe and effective for improving strength in the more-affected limb in people living with hemiparetic stroke. Future work should explore the use of AIH to enhance task-specific training-induced plasticity.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04019522.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"1054-1057"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute-Phase Recording of the Spreading Depolarization Continuum in Aged Nonhuman Primates During Focal Ischemic Stroke.","authors":"Jeremy J Sword, Tyler Sparks, Luca H Debs, Sebastian Major, Suash J Sharma, Michael A Jensen, Debra T Moore-Hill, Karen Barton, Manan Shah, Klepper Alfredo Garcia, Jeffrey A Switzer, David T Blake, Fernando L Vale, Jens P Dreier, Jed A Hartings, Sergei A Kirov","doi":"10.1161/STROKEAHA.124.049417","DOIUrl":"10.1161/STROKEAHA.124.049417","url":null,"abstract":"<p><strong>Background: </strong>Decades of experimental and clinical data revealed that spreading depolarizations (SDs) play a central causal role in the development of cortical lesions after acute brain injury. However, clinical documentation of events at the onset of focal ischemic stroke and during the initial phase of cortical injury development is lacking because electroencephalography monitoring of SD typically starts hours or days later. Here, we used nonhuman primates to map electrophysiological pathology through focal ischemic stroke's onset and acute stage.</p><p><strong>Methods: </strong>Craniotomies were performed over both hemispheres on 4 male and 1 female nemestrina and rhesus macaques aged 23 years to 32 years. Subdural electrode arrays were placed bilaterally over the middle cerebral artery territory, recording from 24 electrodes 1 cm apart on the left cortex and 7 on the right. After 30 minutes of baseline monitoring, the left middle cerebral artery and, in some cases, also the left internal carotid or anterior cerebral arteries were permanently occluded with aneurysmal clips.</p><p><strong>Results: </strong>Repetitive SDs occurred during the next 3 hours, followed by terminal SD during euthanasia. No epileptiform activity was observed in any of the 5 animals. Nonspreading electrical silence developed in the ischemic core within seconds of ischemic onset, followed by terminal SD and SD-initiated negative ultraslow potential after several minutes. These events defined the ischemic core and led to histologically confirmed cell damage. Initial and subsequent transient SDs caused spreading depression of spontaneous activity in the normally perfused surrounding cortex without any signs of histological damage. Cardiocirculatory arrest at the end of experiments first induced nonspreading depression of activity followed by SD and, eventually, the SD-initiated negative ultraslow potential, which indicated brain death.</p><p><strong>Conclusions: </strong>Results in gyrencephalic nonhuman primates hold significant implications for understanding the role of SD in acute brain injury development and for the clinical translation and diagnosis of pathologies manifested in the SD continuum.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"974-986"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Severity and Outcomes in Large Infarcts With Endovascular Therapy: A Post Hoc Analysis of the ANGEL-ASPECT Trial.","authors":"Qixuan Lu, Lina Zheng, Ximing Nie, Mengxing Wang, Wanying Duan, Xin Liu, Zhe Zhang, Miao Wen, Zhonghua Yang, Xinyi Leng, Yuesong Pan, Thanh N Nguyen, Liping Liu","doi":"10.1161/STROKEAHA.124.049315","DOIUrl":"10.1161/STROKEAHA.124.049315","url":null,"abstract":"<p><strong>Background: </strong>Endovascular therapy (EVT) has been proven effective for patients with acute ischemic stroke with large infarcts. This study aimed to explore the impact of clinical severity on the efficacy of EVT in such patients.</p><p><strong>Methods: </strong>This was a post hoc analysis of the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core), a randomized controlled trial that enrolled patients from 46 centers across China between October 2, 2020, and May 18, 2022. These patients had large infarcts (defined as Alberta Stroke Program Early CT Score of 3-5 or infarct-core volume 70-100 mL) due to anterior-circulation large vessel occlusion within 24 hours after stroke onset with a National Institutes of Health Stroke Scale score of 6 to 30. Patients were randomized into either the EVT group or the medical management alone (MM) group. For this analysis, we categorized the patients into 2 subgroups: moderate stroke and severe stroke, based on a baseline National Institutes of Health Stroke Scale score of either <20 or ≥20. The primary outcome was the ordinal 90-day modified Rankin Scale score (0, no symptoms, to 6, death).</p><p><strong>Results: </strong>Among 455 eligible patients, 347 (76.3%) presented with moderate stroke (170 received EVT, 177 underwent MM), and 108 (23.7%) had severe stroke (60 received EVT, 48 underwent MM). A significant shift toward better outcomes in the 90-day modified Rankin Scale distribution was observed in the EVT group compared with the MM group (generalized odds ratio, 1.66 [95% CI, 1.29-2.13]; <i>P</i><0.001) among patients with moderate stroke. However, this was not the case for those with severe stroke (generalized odds ratio, 1.06 [95% CI, 0.54-2.10]; <i>P</i>=0.87), indicating a significant interaction (<i>P</i>=0.03).</p><p><strong>Conclusions: </strong>In patients with acute large infarcts, EVT was associated with improved functional outcomes compared with MM in patients with moderate stroke. However, no significant difference was observed in patients with severe stroke. Therefore, stroke severity should be considered when selecting patients with large infarcts for EVT.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04551664.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"1048-1053"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516754","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":"Recombinant GDF11 Promotes Recovery in a Rat Permanent Ischemia Model of Subacute Stroke.","authors":"Ori S Cohen, Manisha Sinha, Yongting Wang, Tyler Daman, Pi-Chun Li, Catherine Deatherage, Berenice Charrez, Anish Deshpande, Samuel Jordan, Nyasha J Makoni, Katie LeDonne, Christopher J Dale, Laura Ben Driss, Cheryl Pan, Caterina Gasperini, Amy J Wagers, Lee L Rubin, Seth P Finklestein, Mark Allen, Richard T Lee, Anthony Sandrasagra","doi":"10.1161/STROKEAHA.124.049908","DOIUrl":"10.1161/STROKEAHA.124.049908","url":null,"abstract":"<p><strong>Background: </strong>Stroke remains a leading cause of death and disability, underscoring the urgent need for treatments that enhance recovery. GDF11 (growth differentiation factor 11), a member of the TGF-β (transforming growth factor-β) superfamily, is a circulating protein involved in cellular development and tissue repair. GDF11 has gained attention for its potential regenerative properties in aging and disease contexts, making it a candidate for stroke recovery therapies.</p><p><strong>Methods: </strong>The therapeutic benefits of rGDF11 (recombinant GDF11) were evaluated using a rat ischemic stroke model, in which focal cerebral infarcts were induced in 8- to 10-week-old young adult male Sprague-Dawley rats by permanently occluding the proximal right middle cerebral artery. Rats received single or multiple doses of rGDF11 (0.1-4 mg/kg) or vehicle from 24 to 72 hours post-injury. Sensorimotor functions were evaluated, and brain and serum samples were examined to determine the mechanisms of action and identify biomarkers, using immunofluorescence, target-specific ELISAs, and an aptamer-based proteomics platform.</p><p><strong>Results: </strong>We confirmed rGDF11 activity in vitro and in established in vivo mouse models of cardiac hypertrophy and glucose metabolism and assessed the efficacy of rGDF11 treatment in 6 preclinical stroke studies using independent Contract Research Organizations, with all study animals and treatment groups blinded. All 6 studies revealed consistent improvement in sensorimotor outcomes with rGDF11. rGDF11-treated rats showed increased cortical vascularization and radial glia in the ventricular zone. Serum analysis revealed that rGDF11 caused dose-dependent decreases in CRP (C-reactive protein) and identified novel pharmacodynamic biomarkers and pathways associated with potential mechanisms of action of rGDF11.</p><p><strong>Conclusions: </strong>These results demonstrate that systemically delivered rGDF11 enhances neovascularization, reduces inflammation, promotes neurogenesis, and improves sensorimotor function post-injury in a rat model of ischemic stroke. More importantly, these data define an optimized and clinically feasible rGDF11 dosing regimen for therapeutic development in ischemic stroke and identify a panel of candidate pharmacodynamic and mechanistic biomarkers to support clinical translation.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"996-1009"},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256819","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}