Translational Stroke Research最新文献

{"title":"Comprehensive Venous Outflow Evaluation Predicts Stroke Outcome After Optimal Endovascular Ischemic Stroke Treatment.","authors":"Francesco Favruzzo, Lorena Nico, Alvise Fattorello Salimbeni, Marco Falda, Alessandra Pes, Ludovica De Rosa, Matteo Zaccagnino, Federica Viaro, Alessio Pieroni, Stefano Mozzetta, Joseph Domenico Gabrieli, Giacomo Cester, Francesco Causin, David Liebeskind, Claudio Baracchini","doi":"10.1007/s12975-025-01368-8","DOIUrl":"https://doi.org/10.1007/s12975-025-01368-8","url":null,"abstract":"<p><p>Large vessel occlusion (LVO) acute ischemic stroke represents a leading cause of disability despite successful endovascular treatment (EVT). Venous outflow has recently emerged as a potential predictor of functional outcome in ischemic stroke. We aimed to investigate whether a comprehensive venous drainage evaluation is associated with stroke evolution and functional outcome. Prospective study on acute stroke patients with anterior LVO who underwent optimal recanalization from February 2023 to February 2024. Opacification and drainage time of superficial and deep veins were evaluated on digital subtraction angiography sequences. Clinical outcome was functional recovery at 90 days, whereas neuroradiological outcomes were ischemic lesion growth (ILG) and hemorrhagic transformation (HT). Multivariate logistic and linear regression models were performed. 24/50 patients (48%) displayed an unfavorable outcome, 14/50 (28%) a HT, and 28/50 (56%) an ILG. Longer median washout times of the superficial venous system were independently associated with a higher risk of poor functional outcome (aOR = 1.32; 95% CI 1.02-1.79; p = 0.049), ILG (aB = 3.06; SE 1.26; p = 0.020) and HT (aOR = 1.65; 95% CI 1.21-2.47; p = 0.005), and cortical frontal veins were the best predictor within veins' group. Opacification of Labbè and superficial middle cerebral veins predicted only HT (aOR = 0.178; 95% CI 0.026-0.766, p = 0.041) and ILG (aB = 9.78; SE 2.75; p = 0.003), respectively. In this cohort of LVO acute ischemic stroke patients with an optimal recanalization after EVT, qualitative and quantitative aspects of venous outflow were independent predictors of stroke evolution and functional outcome. A comprehensive venous outflow evaluation represents a potential target for a tailored management of patients after EVT.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjunctive Human Urinary Kallidinogenase Enhances the Cognitive and Hemodynamic Outcomes of Anterior Circulation Stenting.","authors":"Liuting Hu, Fan Yang, Wenjin Shang, Jing Yang, Xinran Chen, Shuangquan Tan, Hongbing Chen, Jian Zhang, Shihui Xing, Yuhua Fan","doi":"10.1007/s12975-025-01375-9","DOIUrl":"https://doi.org/10.1007/s12975-025-01375-9","url":null,"abstract":"<p><p>Chronic cerebral hypoperfusion due to anterior circulation stenosis contributes to cognitive decline. This study examined whether preoperative human urinary kallidinogenase (HUK) administration improves outcomes following percutaneous transluminal angioplasty with stenting (PTAS). In this prospective non-randomized controlled trial, 128 patients with severe anterior circulation stenosis were included in the HUK and control groups, respectively. The primary endpoint was change in Mini-Mental State Examination (MMSE) score at 90 days. Secondary outcomes included changes in Montreal Cognitive Assessment (MoCA) and National Institutes of Health Stroke Scale (NIHSS) scores, perfusion parameters, and inflammatory biomarkers. Propensity score adjustments addressed selection bias. Besides mechanical revascularization by PTAS, HUK pretreatment improved cognitive recovery (ΔMMSE, 5 vs. 2; adjusted p < 0.01) and domain-specific gains in memory, calculation/attention, language, and visuospatial function. HUK significantly promoted postoperative mean transit time (MTT) reduction (1.8 ± 1.3 vs. 0.9 ± 0.6, adjusted p < 0.01), indicating enhanced microcirculatory flow. HUK attenuated ΔIL-6 (18.6 ± 16.2 vs. 26 ± 18, adjusted p = 0.03) and amplified ΔIL-10 (2 ± 0.9 vs. 0.4 ± 0.2, adjusted p < 0.01). Baseline TNF-α predicted cognitive recovery (OR = 0.7, p = 0.03). Safety profiles were comparable (9.4% vs. 10.9% complications, p > 0.05), with no mortality. Collectively, adjunctive HUK administration before PTAS in patients with anterior circulation stenosis was associated with greater cognitive improvement and enhanced microvascular hemodynamics, potentially through anti-inflammatory and perfusion-modulating effects. Larger randomized controlled trials are warranted to validate these associations and elucidate the underlying mechanisms.Trial registration: Chinese Clinical Trial Registry. URL: https://www.chictr.org.cn/ ; unique identifier: ChiCTR2100053351.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Stent-Assisted Versus Non-Stent-Assisted Coiling in the Management of Ruptured Intracranial Aneurysms: A Systematic Review and Meta-Analysis.","authors":"Yu-Hu Ma, Yong-Lin He, Xiao-Yue Zhang, Rui Shang, Hai-Tao Hu, Ting Wang, Sen Lin, Ya-Wen Pan, Chang-Wei Zhang","doi":"10.1007/s12975-024-01314-0","DOIUrl":"10.1007/s12975-024-01314-0","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the safety and efficacy of SAC compared to non-SAC in the treatment of RIA, integrating evidence from high-quality studies to guide clinical practice.</p><p><strong>Methods: </strong>A meta-analysis was conducted to compare SAC with coiling alone and BAC in the treatment of RIA. Primary outcomes were immediate and follow-up aneurysm occlusion rates, along with perioperative hemorrhagic and ischemic complication rates.</p><p><strong>Results: </strong>A total of thirteen retrospective cohort studies were included, comprising 3,086 patients, with 1,078 in the SAC group and 2,008 in the non-SAC group. The immediate complete occlusion rates were similar between the SAC and non-SAC groups (59.1% vs. 61.4%; RR = 1.00; 95% CI [0.94, 1.07]; p = 0.92). However, the SAC group demonstrated a significantly higher long-term complete occlusion rate (61.3% vs. 40.6%; RR = 1.44; 95% CI [1.22, 1.69]; p < 0.001). The incidence of ischemic complications was greater in the SAC group (12.2% vs. 10.0%; RR = 1.68; 95% CI [1.37, 2.07]; p < 0.001), as was the incidence of hemorrhagic complications (7.3% vs. 5.1%; RR = 1.55; 95% CI [1.15, 2.08]; p = 0.004). Perioperative mortality was also elevated in the SAC group (6.7% vs. 6.8%; RR = 1.37; 95% CI [1.00, 1.88]; p = 0.048), with a non-significant trend towards higher long-term mortality (9.8% vs. 9.2%; RR = 1.35; 95% CI [0.98, 1.87]; p = 0.068). Functional outcomes at discharge (76.0% vs. 71.0%; RR = 0.97; 95% CI [0.92, 1.02]; p = 0.237), six months (57.8% vs. 60.8%; RR = 0.93; 95% CI [0.81, 1.07]; p = 0.296), and at the last follow-up (RR = 1.01; 95% CI [0.97, 1.06]; p = 0.592) were comparable between the two groups.</p><p><strong>Conclusions: </strong>SAC significantly improves long-term occlusion rates for RIA compared to non-SAC, despite a higher incidence of complications. Careful patient selection and optimization of antiplatelet therapy may enhance the safety and efficacy of SAC for RIA treatment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1424-1439"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in the Glymphatic System and Association with Brain Structure and Cognitive Function in Moyamoya Disease.","authors":"Huan Zhu, Chenyu Zhu, Tong Liu, Peijiong Wang, Wenjie Li, Qihang Zhang, Yahui Zhao, Tao Yu, Xingju Liu, Qian Zhang, Jizong Zhao, Yan Zhang","doi":"10.1007/s12975-024-01296-z","DOIUrl":"10.1007/s12975-024-01296-z","url":null,"abstract":"<p><p>The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system's role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1173-1184"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Strategies for Targeting Arteriogenesis and Angiogenesis After Stroke.","authors":"Jing Wang, Taoying Xiong, Qisi Wu, Xinyue Qin","doi":"10.1007/s12975-024-01291-4","DOIUrl":"10.1007/s12975-024-01291-4","url":null,"abstract":"<p><p>The interdependence between arteriogenesis and angiogenesis is crucial for enhancing perfusion by synchronously improving leptomeningeal collaterals (LMCs) and microvascular networks after stroke. However, current approaches often focus on promoting arteriogenesis and angiogenesis separately, neglecting the potential synergistic benefits of targeting both processes simultaneously. Therefore, it is imperative to consider both arteriogenesis and angiogenesis as integral and complementary strategies for post-stroke revascularization. To gain a deeper understanding of their relationships after stroke and to facilitate the development of targeted revascularization strategies, we compared them based on their timescale, space, and pathophysiology. The temporal differences in the occurrence of arteriogenesis and angiogenesis allow them to restore blood flow at different stages after stroke. The spatial differences in the effects of arteriogenesis and angiogenesis enable them to specifically target the ischemic penumbra and core infarct region. Additionally, the endothelial cell, as the primary effector cell in their pathophysiological processes, is promising target for enhancing both. Therefore, we provide an overview of key signals that regulate endothelium-mediated arteriogenesis and angiogenesis. Finally, we summarize current therapeutic strategies that involve these signals to promote both processes after stroke, with the aim of inspiring future therapeutic advances in revascularization.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1383-1399"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease.","authors":"Kikutaro Tokairin, Masaki Ito, Alex G Lee, Mario Teo, Shihao He, Michelle Y Cheng, Gary K Steinberg","doi":"10.1007/s12975-024-01299-w","DOIUrl":"10.1007/s12975-024-01299-w","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a chronic cerebrovascular disorder that can lead to stroke and neurological dysfunctions. Given the largely sporadic nature and the role of gene-environment interactions in various diseases, we examined epigenetic modifications in MMD. We performed genome-wide DNA methylation using Illumina 850 K Methylation EPIC BeadChip, in two racially distinct adult female cohorts: a non-Asian cohort (13 MMD patients and 7 healthy controls) and an Asian cohort (14 MMD patients and 3 healthy controls). An additional external cohort with both sexes (females: 5 MMD patients and 5 healthy controls, males: 5 MMD patients and 5 healthy controls) was included for validation. Our findings revealed strikingly low DNA methylation variability between MMD patients and healthy controls, in both MMD female cohorts. In the non-Asian cohort, only 6 probes showed increased variability versus 647 probes that showed decreased variability. Similarly, in the Asian cohort, the MMD group also displayed a reduced methylation variability across all 2845 probes. Subsequent analysis showed that these differentially variable probes are located on genes involved in key biological processes such as methylation and transcription, DNA repair, cytoskeletal remodeling, natural killer cell signaling, cellular growth, and migration. These findings mark the first observation of low methylation variability in any disease, contrasting with the high variability observed in other disorders. This reduced methylation variability in MMD may hinder patients' adaptability to environmental shifts, such as hemodynamic stress, thereby influencing vascular homeostasis and contributing to MMD pathology. These findings offer new insights into the mechanisms of MMD and potential treatment strategies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1198-1213"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.","authors":"Inmaculada Díaz-Maroto, Beatriz Castro-Robles, Miguel Villar, Jorge García-García, Óscar Ayo-Martín, Gemma Serrano-Heras, Tomás Segura","doi":"10.1007/s12975-024-01283-4","DOIUrl":"10.1007/s12975-024-01283-4","url":null,"abstract":"<p><p>Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10 years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9 h) and at 24 and 72 h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72 h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72 h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24 h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1094-1105"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: An Alternative Photothrombotic Model of Transient Ischemic Attack.","authors":"Y N Kalyuzhnaya, A K Logvinov, S G Pashkevich, N V Golubova, E S Seryogina, E V Potapova, V V Dremin, A V Dunaev, S V Demyanenko","doi":"10.1007/s12975-024-01287-0","DOIUrl":"10.1007/s12975-024-01287-0","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1441"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perihematomal Neurovascular Protection: Blocking HSP90 Reduces Blood Infiltration Associated with Inflammatory Effects Following Intracerebral Hemorrhage in Rates.","authors":"Di Hu, Chao Yan, Hesong Xie, Xueyi Wen, Kejing He, Yan Ding, Ying Zhao, Heng Meng, Keshen Li, Zhenguo Yang","doi":"10.1007/s12975-024-01289-y","DOIUrl":"10.1007/s12975-024-01289-y","url":null,"abstract":"<p><p>The active hemorrhage surrounding the hematoma is caused by the infiltration of blood into the cerebral parenchyma through the ruptured vessel, including the compromised blood-brain barrier (BBB). This process is thought to be mainly driven by inflammation and serves as a significant pathological characteristic that contributes to the neurological deterioration observed in individuals with intracerebral hemorrhage (ICH). Heat shock protein 90 (HSP90) exhibits abnormally high expression levels in various diseases and is closely associated with the onset of inflammation. Here, we found that blocking HSP90 effectively alleviates the inflammatory damage to BBB and subsequent bleeding around the hematoma. We have observed increased HSP90 levels in the serum of patients with ICH and the perihematoma region in ICH rats. Treatment with anti-HSP90 drugs (Geldanamycin and radicicol) effectively reduced HSP90 levels, resulting in enhanced neurological outcomes, decreased hematoma volume, and prevented peripheral immune cells from adhering to the BBB and infiltrating the brain parenchyma surrounding the hematoma in ICH rats. Mechanistically, anti-HSP90 therapy alleviated BBB injury caused by ICH-induced inflammation by suppressing TLR4 signaling. The study highlights the potential of anti-HSP90 therapy in mitigating BBB disruption and hemorrhage surrounding the hematoma, providing new insights into the management of ICH by targeting HSP90.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1133-1145"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease.","authors":"Grace Prochilo, Chuanlong Li, Eleni Miliotou, Russell Nakasone, Alissa Pfeffer, Charles Beaman, Naoki Kaneko, David S Liebeskind, Jason D Hinman","doi":"10.1007/s12975-024-01310-4","DOIUrl":"10.1007/s12975-024-01310-4","url":null,"abstract":"<p><p>Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1301-1316"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}