Translational Stroke Research最新文献

{"title":"Correction to: The Cerebrovascular Reactivity Adjusted Fractional Amplitude of Low-Frequency Fluctuations Abnormalities in Middle Cerebral Artery Stenosis and Occlusive Disease.","authors":"Liqing Zhang, Luoyu Wang, Xue Tang, Yidi Zhu, Rong Wang, Zhongxiang Ding","doi":"10.1007/s12975-026-01466-1","DOIUrl":"10.1007/s12975-026-01466-1","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362438","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":"Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Swallowing Function in Post-stroke Dysphagia: A Randomized Controlled Study.","authors":"E Chang, Yujuan Jiang, Jiongmei Wang","doi":"10.1007/s12975-026-01469-y","DOIUrl":"10.1007/s12975-026-01469-y","url":null,"abstract":"<p><p>Post-stroke dysphagia (PSD) is a common and disabling complication of stroke. Conventional swallowing rehabilitation provides limited benefit for patients with moderate-to-severe PSD, especially those with impaired neuromuscular activation. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a non-invasive neuromodulatory approach that may enhance swallowing recovery, yet its clinical efficacy and underlying mechanisms remain to be clarified. A total of 96 patients with PSD were randomly assigned to a control group (conventional swallowing rehabilitation) or a taVNS group (conventional rehabilitation + taVNS). After a 4-week intervention, 86 patients completed the study (Control: n = 44; taVNS: n = 42). Clinical swallowing outcomes (FOIS, SSA, PAS), swallowing-related surface electromyography (Aemg, Iemg, reverse activation proportion, EMG latency), and serum biomarkers (BDNF, GFAP, IL-6) were assessed before and after treatment. Both groups exhibited improved swallowing function after intervention; however, the taVNS group showed significantly greater improvement in FOIS (p < 0.001), SSA (p < 0.001), and PAS (p = 0.001) compared with the control group. The taVNS group also demonstrated larger increases in Aemg and Iemg, greater reductions in reverse activation proportion, and shorter EMG latency (all p < 0.05). Serum BDNF levels increased more prominently in the taVNS group, whereas GFAP and IL-6 levels showed significantly greater reductions (all p < 0.01), with large to moderate-large effect sizes for key outcomes (FOIS: Cohen's d = 0.69, 95%CI [0.42,0.82]; SSA: d = 0.64, 95%CI [-5.28,-1.74]; BDNF: d = 1.36, 95%CI [2.33,3.77]; IL-6: d = 0.91, 95%CI [-16.65,-7.99]). taVNS combined with conventional rehabilitation was associated with greater swallowing improvements. However, due to feasibility constraints in moderate-to-severe PSD patients, a sham control was not included; therefore, causal attribution specifically to vagus nerve activation remains preliminary. The observed changes in serum biomarkers (increased BDNF, decreased GFAP and IL-6) are exploratory parallel associations and do not constitute mechanistic proof of central nervous system effects.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353773","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":"Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.","authors":"François Delvoye, Julie Lebeau, Cécile Oury, Céline D'Emal, Bernard Lambermont, Nathalie Layios, Didier Ledoux, Annie Dubuisson, Louis Deprez, Martin Moïse, Benoit Ho-Tin-Noé, Mikael Mazighi, Nicolas Engrand, Jean-Philippe Désilles, Benjamin Maïer","doi":"10.1007/s12975-026-01461-6","DOIUrl":"10.1007/s12975-026-01461-6","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) remains associated with substantial morbidity and mortality despite best medical treatment. Increasing evidence implicates thrombo-inflammation (TI), driven by neutrophils and neutrophil extracellular traps (NETs), in the pathogenesis of delayed cerebral ischemia (DCI) and cognitive impairment. This narrative review summarizes experimental and clinical data linking neutrophil activation and NETs formation to DCI after aSAH and outlines emerging therapeutic strategies. This review was structured according to the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines and followed general recommendations for narrative reviews. A comprehensive PubMed and clinicaltrials.gov search identified experimental and clinical studies published in English without time window, focusing on TI, neutrophil activation, or NETosis in the acute phase of aSAH. Past and ongoing clinical trials were classified by mechanism of action. Experimental models and human data show early and sustained neutrophil activation within cerebral and systemic compartments after aSAH. NETs promote microvascular thrombosis, blood-brain barrier disruption, microglial activation, and neuronal injury, ultimately contributing to DCI and long-term cognitive impairment. Outside the brain, NETs may also aggravate neurogenic pulmonary edema and cardiac dysfunction. In animal models, deoxyribonuclease I (DNase I) effectively degrades NETs, improving perfusion, limiting neuronal apoptosis, and enhancing recovery. Several ongoing trials target TI pathways, including the RESET trial, which evaluates the impact of IV DNase I on clinical outcome after aSAH. NETs produced after neutrophil activation may be central to DCI. Targeting NETs represents a promising translational path to improve cerebral and systemic outcomes after aSAH.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353762","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":"Multiscale Mechanisms that Underlie Intermittent Theta-burst Stimulation in Post-stroke Motor Recovery: From Molecular Signaling to Network Reorganization.","authors":"Cheng Xie, Yan Hua, Xiuli Sun, Yulong Bai","doi":"10.1007/s12975-026-01467-0","DOIUrl":"10.1007/s12975-026-01467-0","url":null,"abstract":"<p><p>Although intermittent theta-burst stimulation (iTBS) has emerged as a promising time-efficient and non-invasive neuromodulatory strategy in post-stroke motor rehabilitation, its clinical efficacy remains variable across patients and studies. In this review, we propose a multiscale framework for understanding how iTBS may support post-stroke motor recovery while emphasizing the current limits of translational evidence. At the microscopic and mesoscopic levels, preclinical studies suggest that iTBS contributes to early post-stroke repair by modulating ferroptosis, endoplasmic reticulum stress-related apoptosis, pyroptosis, neuroimmune responses involving astrocytes, white matter integrity, neurovascular remodeling, and neurotrophic signaling. These mechanisms are acknowledged to provide a biological substrate for post-stroke plasticity. At the clinical neurophysiological and neuroimaging levels, the available human studies indicate that iTBS modulates corticospinal excitability, cortical oscillatory dynamics, interhemispheric interactions, and large-scale motor-network organization. We herein further discuss the determinants of treatment variability, including stroke stage, lesion location, corticospinal tract integrity, baseline impairment severity, stimulation target, dosage parameters, co-interventions, genetic polymorphisms, and endogenous brain state. Current evidence remains limited due to small-sample size, heterogeneous protocols, incomplete safety and dose reporting, and temporal and geographic concentrations of the available studies. We posit that investigators in their future studies prioritize standardized reporting, multicenter and internationally diverse trials, biomarker-guided stratification, individualized electric-field modeling, and closed-loop stimulation strategies. Overall, iTBS remains a promising but protocol-sensitive and patient-dependent intervention, and this review provides a hypothesis-generating framework for future mechanistic and clinical studies in post-stroke motor rehabilitation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340220","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":"IGF-1 Inhibits the Hemodynamics‑Induced Progression of Intracranial Aneurysms by Modulating the Proliferation and Apoptosis of Vascular Smooth Muscle Cells.","authors":"Si-Si Li, Zhi-Wen Lu, Yin Luo, Hai-Shuang Tang, Bo Hong, Yu Zhou, Jian-Min Liu","doi":"10.1007/s12975-026-01462-5","DOIUrl":"10.1007/s12975-026-01462-5","url":null,"abstract":"<p><p>Abnormal shear stress is closely linked to the progression of intracranial aneurysms (IAs) and the apoptosis of middle layer of vascular wall. Insulin-like growth factor-1 (IGF-1) is crucial for vascular protection by inhibiting local vascular cell apoptosis; however, its involvement in the pathology of IAs remains unclear. Eight human IAs and 8 superficial temporal artery (STA) samples were collected for high-throughput sequencing to analyze the expression of IGF-1. IA mouse models were established to evaluate the effect of IGF-1 on the aneurysmal remodeling of the cerebral arteries. We conducted a comprehensive analysis of the Circle of Willis in mice using pathological and proteomic methods to assess the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Additionally, vessel perfusion was perfomed to evaluate the incidence of IAs in mouse model. In vitro, mouse VSMCs and endothelial cells (ECs) of aorta were extracted, and a co-culture model with a flow chamber was established to simulate a laminar flow environment. The relationship between wall shear stress (WSS) gradient and the expression of IGF-1 was explored. Then the proliferation and apoptosis of VSMCs, and the related signaling pathway was determined by CCK8, flow cytometry, immunoblotting analysis and chromatin immunoprecipitation. Both IGF-1 and IGF-1R was downregulated in human IAs. High WSS reduced VSMC IGF-1 expression, facilitated apoptosis in VSMCs, and suppressed their proliferation. Over expression of IGF-1 promoted VSMC proliferation and inhibited apoptosis both in vivo and in vitro. Moreover, increased IGF-1 expression reduced mouse IA incidence. Mechanistically, IGF-1 regulated high WSS-induced apoptosis and proliferation of VSMCs via the PI3K/AKT signaling pathway. Furthermore, elevated WSS was found to suppress the expression of FOXM1, which subsequently modulates the expression of IGF-1. High WSS downregulates the expression of IGF-1 in VSMCs, thereby inhibiting its proliferative and anti-apoptotic effects, which ultimately contributes to the IA progression via PI3K/AKT signaling pathway. Furthermore, FOXM1 played a role in this process by targeting IGF-1.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319250","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":"Choroidal Changes in Cerebral Amyloid Angiopathy Studied by Optical Coherence Tomography Angiography.","authors":"Jiahe Ye, Xiaodong Ye, Yuchao Jia, Xianxian Li, Xin Liu, Suiqiang Zhu, Shanshan Huang","doi":"10.1007/s12975-026-01463-4","DOIUrl":"10.1007/s12975-026-01463-4","url":null,"abstract":"<p><p>Background cerebral amyloid angiopathy (CAA) involves amyloid-β deposition in cerebral vessels. Its effects on the ocular circulation remain unclear. Using swept-source optical coherence tomography angiography (SS-OCTA), this study quantitatively characterized choroidal parameters in CAA patients and their correlation with MRI neuroimaging markers. Method CAA patients and matched controls were enrolled. We used SS-OCTA to obtain choroidal parameters including thickness, choriocapillaris flow density, choroidal vascular volume (CVV), and choroidal vascular index (CVI). The correlations between these parameters and CAA-specific neuroimaging markers on MRI were then analyzed. Results in the study comprising 23 eyes from 23 CAA patients and 23 eyes from 23 healthy controls, we interrogated choroidal parameters using SS-OCTA. The CAA group exhibited a significantly lower choriocapillaris flow density compared to controls (P < 0.05). Furthermore, this parameter showed a nominal inverse association with the burden of subcortical spot white matter hyperintensities, which did not survive correction for multiple comparisons (FDR-adjusted q > 0.05). Conclusion our study suggests that reduction in choriocapillaris density may serve as a potential cross-sectional biomarker for CAA, pending validation in longitudinal studies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266158","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":"Pedagogy and Enriched Environment for Rehabilitation in the HOME After Stroke (PEER-HOMEcare): Study Protocol for a Single-Group Feasibility Study.","authors":"Arve Opheim, Luca Oppici, Ann Marie Hestetun-Mandrup, Katharina S Sunnerhagen, Lena Rafsten, Guna Bērziņa, Agnese Kārkliņa, Marianne Løvstad, Hege Prag Øra, Lauren Marcos, Matheus Pacheco, Aléxia Fernandes, Linda Sørensen, James Robert Rudd","doi":"10.1007/s12975-026-01459-0","DOIUrl":"10.1007/s12975-026-01459-0","url":null,"abstract":"<p><p>Home-based rehabilitation after stroke is increasingly important, as pressure on hospital services rise and recovery occurs mostly at home. Enriching the home (Environmental Enrichment, EE) represents a potential strategy to support rehabilitation by providing continuous task- and context-specific stimulation that promotes functional recovery through frequent and exploratory use of the affected arm. Exploratory behaviour - self-initiated, varied and adaptive movements - is an important driver of motor learning and neuroplasticity. While strong evidence from animal research demonstrates the benefits of EE for functional recovery, translation to human home-based rehabilitation remains limited. This study will investigate the feasibility of the Pedagogy and Enriched Environment for Rehabilitation in the HOME after stroke (PEER-HOMEcare) intervention. PEER-HOMEcare translates EE by introducing meaningful, targeted and progressive home modifications to promote exploratory use of the affected arm during daily activities. In this prospective, single group, experimental study, 45 stroke survivors (≥ 18 years), within 6 months post-stroke across Norway, Sweden and Latvia will participate. Wearable sensors will be used to capture exploratory behaviour and activity patterns, giving objective insights to inform progressive modifications to the home. Primary outcomes of feasibility and acceptability will be assessed through questionnaires, logs and interviews. Intervention fidelity, participant adherence and adverse events will be evaluated. Secondary outcomes include changes in arm function, self-perceived activities of daily living and psychosocial outcomes. This study will provide important knowledge about the feasibility of an innovative EE approach for home-based rehabilitation, informing a future trial evaluating its clinical effectiveness. Trial registration in https://www.ClinicalTrials.gov on 06-04-2026, NCT07517120.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13272276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259697","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":"Temporal Pattern and Clinical Value of Serum GFAP in Acute Ischemic Stroke: Results from Two Prospective German Cohorts.","authors":"Lorenzo Barba, Christoph Vollmuth, Patrick Oeckl, Steffen Halbgebauer, Christian Hametner, Fabian Essig, Peter U Heuschmann, Alexander M Kollikowski, Mirko Pham, Michael K Schuhmann, Petra Steinacker, Yashar Bahramsari, Annemarie Thaele, Caroline Kulitze, Samir Abu-Rumeileh, Karl Georg Haeusler, Guido Stoll, Hermann Neugebauer, Markus Otto","doi":"10.1007/s12975-026-01458-1","DOIUrl":"10.1007/s12975-026-01458-1","url":null,"abstract":"<p><p>Serum glial fibrillary acidic protein (sGFAP) is an astroglial biomarker preliminarily investigated in acute ischemic stroke (AIS). We aimed to investigate its temporal pattern and clinical value in two German AIS cohorts. Using immunoassay, we measured sGFAP concentrations in 952 samples of 572 AIS patient and 32 samples of controls recruited in Halle [AIS n = 102, age: 70.9 (± 15.9) years, 52.0% males; controls n = 32, age: 47.6 (± 18.8) years, 59.4% males] and Würzburg [AIS n = 470, age 74.6 (± 12.8) years, 48.3% males]. In AIS patients, we stratified samples according to the time from symptom onset to blood sampling, namely at D1 (< 24 h), D2 (24-48 h), D3 (48-72 h) and D5-7 (96-144 h), and tested associations between biomarker levels and clinical data. sGFAP level was increased at all timepoints after AIS compared to control subjects (p < 0.001, age-adjusted p < 0.01) with significant changes over time (D1 < D2< D3 ≥ D5-7). We found increased sGFAP concentrations in AIS patients who had altered mental status on admission (p < 0.01), hemorrhagic transformation of AIS (HT, p < 0.001) as well as systemic infections such as pneumonia (p < 0.001). Higher D1 sGFAP concentrations were associated with higher likelihood of modified Rankin Scale > 2 at 3 months [aOR = 1.015 (95%CI = 1.005-1.025), p = 0.004] and a shorter survival at longest follow-up (median: 576 days, max 922 days) [highest tertile vs. lowest tertile HR = 2.94 (95%CI = 1.21-7.17), p = 0.018]. sGFAP is elevated after AIS and of informative value regarding the risk HT and infections, as well as on the clinical outcome at follow-up.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253334","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":"Intermittent Hypoxia Maintains Neovascular Blood-Brain Barrier Integrity Via the HIF-1α/VEGFB Axis.","authors":"Mingxuan Cao, Zirui Xu, Yakun Gu, Qihan Zhang, Mengyuan Guo, Zhengming Tian, Feiyang Jin, Qianqian Shao, Xiuhai Guo, Jia Liu, Xunming Ji","doi":"10.1007/s12975-026-01454-5","DOIUrl":"10.1007/s12975-026-01454-5","url":null,"abstract":"<p><p>Ischemic stroke (IS) is the most prevalent cerebrovascular disease, with a high proportion of patients developing lifelong disability. Cerebral microcirculatory dysfunction is a key driver of poor IS prognosis. Hypoxia-induced cerebral angiogenesis could improve cerebral perfusion but risks blood-brain barrier (BBB) disruption, worsening outcomes. We previously found that intermittent hypoxia (IH) promotes cerebral angiogenesis and improves IS outcomes, but whether it maintains BBB integrity during angiogenesis and the underlying mechanism remains unclear. This study established mouse hypoxia models, including IH and continuous hypoxia (CH) treatment groups. We found that both IH and CH transiently increased cerebrovascular permeability via angiogenesis activation. However, IH restored permeability to baseline over time, with astrocyte end-foot wrapping, pericyte coverage, and tight junction protein ZO-1 level in neovessels comparable to controls. In contrast, CH failed to recover vascular leakage and BBB integrity within the same period. Mechanistically, IH uniquely activated both hypoxia-inducible factor (HIF)-1α and HIF-2α, while CH only activated HIF-2α. HIF-1α-specific activation in the IH group promoted downstream vascular endothelial growth factor (VEGF)-B transcription, which antagonized VEGFA-mediated endothelial barrier disruption and adhesion molecule upregulation. This study demonstrates that IH maintains neovascular BBB integrity via the HIF-1α/VEGFB pathway, providing a theoretical basis for novel IS interventions and targeted drug development.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240242","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":"AI-Guided Patient-Derived Endothelial Modeling Identifies a Reversible Moyamoya-Specific miRNA Deficiency Corrected by Stem Cell-Extracellular Vesicles.","authors":"Ji Hoon Bang, Ji Eun Kim, Eun Hee Kim, Hyeock Yang, Jiho Jang, Oh Young Bang","doi":"10.1007/s12975-026-01456-3","DOIUrl":"10.1007/s12975-026-01456-3","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by abnormal vascular remodeling and impaired angiogenesis. We profiled plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) from MMD patients and healthy controls and generated patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to investigate disease-associated molecular alterations and therapeutic reversibility. Both plasma EVs and iPSC-ECs from MMD patients showed significant depletion of angiogenesis-related miRNAs. Small RNA sequencing data revealed mesenchymal stem cell-derived EVs (MSC-EVs) contain a miRNA repertoire that substantially overlaps with miRNAs deficient in MMD. Treatment of MMD iPSC-ECs with MSC-EVs restored the majority of the depleted miRNAs to normal levels, normalized predicted target mRNA expression, and rescued angiogenic function in a dose-dependent manner, as demonstrated by tube formation assays. To improve identification of biologically relevant miRNA-mRNA interactions, we developed an artificial intelligence-based framework integrating experimentally validated databases, endothelial-focused literature mining, and large language model (LLM)-assisted mechanistic scoring. Incorporation of LLM-derived contextual features modestly improved prediction performance compared with conventional sequence-based models (baseline AUROC ~ 0.51; LLM-enhanced AUROC ~ 0.72), suggesting that literature-informed biological context provides meaningful signal beyond structural target features alone. Furthermore, our findings demonstrate that MSC-EV therapy can substantially reverse molecular and functional endothelial deficits. Integrated profiling and AI-driven interaction mapping together establish a hypothesis-generating framework (\"Exo-Courier\") for biologically informed prioritization of EV-based therapeutic targets in vascular disorders.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219857","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}