Translational Stroke Research最新文献

{"title":"Lesion Water Content on CT Predicts 12-Month Outcome and Modifies Thrombectomy Effect in Large-Core Stroke-A Secondary Analysis of the TENSION Trial.","authors":"Gabriel Broocks, Martin Bendszus, Sophia Hohenstatt, Claus Z Simonsen, Götz Thomalla, Elke R Gizewski, Anne Hege Aamodt, Antonin Krajina, Laurent Pierot, Kamil Zeleňák, Blanca Fuentes, Michael D Hill, Andre Kemmling, Lieselotte Vandewalle, Anke Wouters, Robin Lemmens, Jelle Demeestere, Wim H van Zwam, Julie Staals, Susanne Gellißen, Jens Fiehler, Laurens Winkelmeier, Lukas Meyer, Helge Kniep","doi":"10.1007/s12975-026-01501-1","DOIUrl":"https://doi.org/10.1007/s12975-026-01501-1","url":null,"abstract":"<p><p>In large-core ischemic stroke, outcomes after thrombectomy remain heterogeneous, and imaging markers that capture treatment-modifiable injury beyond lesion extent are needed. We investigated whether lesion water content on noncontrast CT, quantified as net water uptake (NWU), predicts 12-month functional outcome and modifies the effect of endovascular thrombectomy (EVT). This secondary analysis of the randomized TENSION trial included 198 patients with admission CT suitable for NWU quantification and available 12-month modified Rankin Scale (mRS) scores; 168 had paired 24-h CT for follow-up NWU (NWUFU) assessment. The primary outcome was ordinal 12-month mRS. Multivariable ordinal and logistic regression tested associations and the NWU × EVT interaction, with discrimination assessed by area under the receiver operating characteristic curve (AUC). Median baseline NWU was 16.4% and NWUFU 28.9%. At 12 months, 45 patients (23%) had mRS 0-3 and 111 (56%) had died. Higher baseline NWU independently predicted worse 12-month mRS (adjusted common odds ratio [acOR], 1.10 per percentage-point; 95% CI, 1.05-1.16; P < 0.001) and modified the EVT effect (interaction acOR, 1.17; 95% CI, 1.06-1.30; P = 0.002), with greater discrimination than ASPECTS. NWUFU was the strongest single imaging predictor (acOR, 1.10; 95% CI, 1.06-1.14; P < 0.001; AUC, 0.78 for mRS 0-3) and superseded baseline NWU when co-modeled. Among 97 90-day survivors, higher NWUFU independently predicted late mortality (adjusted odds ratio, 1.09; 95% CI, 1.02-1.18; P = 0.019). Lesion water content may therefore provide a clinically accessible CT biomarker linking treatment-modifiable injury at baseline with realized post-treatment injury and long-term outcome.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246125","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":"Proteome-Wide Mendelian Randomization Identifies Therapeutic Targets for Ischemic Stroke.","authors":"Kangjia Song, Chao Li, Mingchao Shi, Shuang Qi","doi":"10.1007/s12975-026-01509-7","DOIUrl":"https://doi.org/10.1007/s12975-026-01509-7","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke carries substantial residual risk despite acute revascularization and secondary prevention, and small-vessel disease (SVD) lacks specific preventive therapy. Mendelian randomization (MR) using cis-acting protein quantitative trait loci (pQTLs) identifies circulating proteins whose lifelong modulation alters stroke risk.</p><p><strong>Methods: </strong>We screened 589 conditionally independent cis-pQTLs from the INTERVAL study against four GIGASTROKE outcomes: any ischemic stroke (AIS), large-artery atherosclerosis (LAA), cardioembolic stroke (CES), and SVD. Wald ratio estimates were corrected by Benjamini-Hochberg false discovery rate (FDR) within each outcome, with a pooled cross-outcome correction as a sensitivity analysis. FDR-significant associations underwent colocalization (approximate Bayes factor; H4 > 0.80), replication in the independent deCODE pQTL cohort, cell-type expression validation in a human brain vascular single-nucleus atlas (65,479 nuclei), and phenome-wide safety screening.</p><p><strong>Results: </strong>Ten protein-outcome associations reached FDR < 0.05; nine replicated in deCODE and eight colocalized at H4 > 0.80, with two further pairs (ABO-LAA, cyclin H-CES) in the suggestive range (H4 0.70-0.80). For SVD, higher SPATA20 raised risk (OR 1.47, 95% CI 1.24-1.73, p = 5.3 × 10⁻⁶), and higher KDELC2 lowered risk (OR 0.82, 95% CI 0.74-0.91, p = 2.2 × 10⁻⁴). A protective cyclin H signal for CES passed outcome-wise FDR (q = 0.046) but not the pooled correction (q = 0.059) and is reported as preliminary. ABO, MMP-12, and SWAP70 confirmed earlier reports; SCARA5 failed colocalization and replication and was excluded. Colocalization confirmed the lead liabilities for MMP-12 (atopic dermatitis, two cohorts) and SWAP70 (rheumatoid arthritis) as on-target effects; two further liability associations (allergic asthma, ER-negative breast cancer) did not meet the colocalization threshold and remain hypothesis-generating.</p><p><strong>Conclusions: </strong>Proteome-wide MR prioritizes two SVD-associated proteins: SPATA20 (risk-raising; now independently confirmed across screens) and KDELC2 (protective; newly reported). Both require replication on orthogonal proteomic platforms and functional validation before therapeutic development.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246073","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 Transcriptomic and Single-Cell Sequencing Identifies Altered Expression of Circadian Rhythm-Related Genes Pomc and Bmp4 in Post-Stroke Depression.","authors":"Yuntai Wang, Jing Li, Yihuan Yuan, Chuanfei Liu, Dan Luo, Yang Li, Wei Chen, Zhuoze Wu","doi":"10.1007/s12975-026-01507-9","DOIUrl":"https://doi.org/10.1007/s12975-026-01507-9","url":null,"abstract":"<p><p>Post-stroke depression (PSD) is a serious complication that significantly hinders stroke patients' recovery and quality of life. Uncovering the molecular changes that drive PSD is vital for understanding how depression develops following a stroke. In this study, we established a reproducible PSD model using minimally invasive photochemical-induced focal cortical lesion. Transcriptomic sequencing demonstrated that dysregulation of circadian entrainment genes is a central pathway in the development of post-stroke depressive-like behaviors. Protein-protein interaction network analysis of these circadian rhythm-related genes identified six hub genes. Four of these, including Pomc and Bmp4, exhibited expression patterns consistent with experimental validation. Integrated single-cell transcriptomic analysis further pinpointed cell-type-specific expression abnormalities of Pomc in endothelial cells and Bmp4 in oligodendrocytes. Subsequently, in silico perturbation analysis further indicated that their shared underlying regulatory mechanisms involve cell adhesion and extracellular matrix interaction. Collectively, using transcriptomic and single-cell sequencing in a PSD model, this study revealed altered expression patterns of circadian rhythm-related genes, providing potential targets for further investigation into the pathogenesis of PSD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228677","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":"Long-Term Quantitative MRI and Quality-of-Life After Endovascular Therapy in Acute Ischemic Stroke - A MR CLEAN-NO IV Substudy.","authors":"Praneeta R Konduri, Dimitrios Karkalousos, Alexandra de Sitter, Manon Kappelhof, Maarten M H Lahr, Chi P Nguyen, Aad van der Lugt, Yvo B Roos, Jonathan M Coutinho, Henk A Marquering, Charles B L M Majoie, Bart J Emmer, Luka C Liebrand, Matthan W A Caan","doi":"10.1007/s12975-026-01497-8","DOIUrl":"10.1007/s12975-026-01497-8","url":null,"abstract":"<p><p>This study aims to explore the long-term evolution of endovascular treatment after acute ischemic stroke (AIS) using quantitative MRI, and its relationship with quality of life (QoL). In this long-term substudy of patients from the MR CLEAN-NO IV trial, patients were included who received 24-hour post-stroke MRI and were functionally independent 90 days after stroke onset. Patients underwent a quantitative MRI exam three years after stroke onset to measure focal volume loss, myelin damage, iron deposition, and atrophy within and around the ischemic lesion seen on 24-hour-MRI, in addition to a QoL assessment. Bayesian statistical analyses were used to assess MRI measures lateralized to the ipsilateral hemisphere and to evaluate the relationship of these measures with baseline and treatment characteristics along with QoL. The Bayes Factor (BF) reflected moderate, strong or very strong evidence (BF = 3.0;20;1.5⋅10² respectively). In the 24 included patients, prominent focal volume loss, iron deposition, ventricular enlargement and myelin damage (BF:2.0⋅10²) were observed peripheral to the initial 24-hour DWI lesion at long-term FU MRI. In the basal ganglia nuclei, very strong evidence of focal volume loss (BF > 8.1⋅10²) and moderate to very strong evidence of iron deposition (BF: 5.0 to 2.7⋅10²) were observed at long-term assessment. Higher systolic blood pressure was associated with reduced long-term ventricular atrophy (BF:5.8). Long-term differences in ipsilateral versus contralateral hippocampal volume difference (BF:8.0) and iron deposition (BF:4.1) were moderately associated with QoL. Long-term subtle yet widespread demyelination and iron deposition were observed, and these changes correlated with long-term recovery.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164991","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":"Acute Ischaemic Stroke: Therapeutic Targets and Key Modulators of the Fibrinolytic System and Clot Formation.","authors":"Oshi Swarup, Anna H Balabanski, Geoffrey C Cloud, Robert L Medcalf","doi":"10.1007/s12975-026-01502-0","DOIUrl":"10.1007/s12975-026-01502-0","url":null,"abstract":"<p><p>The processes of clot formation and clot dissolution with fibrinolysis underpin the pathophysiological mechanisms of acute ischaemic stroke (AIS) and its treatment. Detailed understanding of the modulation of this system is required to develop effective and safe stroke therapeutics. Clot formation occurs with the interaction of the coagulation cascade, along with platelets and fibrin meshwork. Conversely, fibrinolysis involves the serine protease plasmin, its zymogen, plasminogen and its enzymatic conversion by tissue plasminogen activator. The regulators and inhibitors that modulate the interactions in clot formation and fibrinolysis can be potential targets for new and emerging stroke therapies. The aim of this narrative review is to help inform stroke clinicians and researchers about the role of the fibrinolytic system and its inhibitors in AIS and the potential for new therapeutic targets. We outline the processes involved in clot formation and dissolution, the role of endogenous inhibitors of the fibrinolytic system, followed by potential therapeutic targets including tissue plasminogen activators as well as novel therapies and adjuncts. Better understanding of these processes will provide insight into the variable response to current stroke fibrinolytics amongst AIS patients and help to develop new and improved AIS therapeutics in future.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171122","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":"Lipid Traits and Risk of Subarachnoid Haemorrhage: A Systematic Review and Mendelian Randomization Study in UK Biobank.","authors":"Frederick Ewbank, Cameron Pinn, Benjamin Gaastra, William Tapper, Ian Galea, Diederik Bulters","doi":"10.1007/s12975-026-01499-6","DOIUrl":"10.1007/s12975-026-01499-6","url":null,"abstract":"<p><p>Lipid traits are established risk factors for atherosclerotic disease; however, their relationship with intracranial aneurysms and subarachnoid haemorrhage (SAH) remains unclear. Recent Mendelian randomisation (MR) studies have reported inconsistent findings. This study aimed to review the literature and assess the association between lipid traits and SAH using a one-sample MR analysis accounting for statin use and nonlinearity. We performed a systematic review of MR studies investigating lipid traits and intracranial aneurysms/SAH. A meta-analysis was not undertaken because studies used overlapping datasets. In parallel, we conducted a one-sample MR analysis of 486,603 UK Biobank participants. Genetic instruments for low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglycerides (TG) were derived from published genome-wide association studies. Associations with SAH were adjusted for lipid-lowering therapy. Nonlinear relationships were explored using cubic splines and piecewise MR. While eight MR studies met the inclusion criteria, seven relied on the same outcome cohort. Despite this, these studies showed no consistent direction of effect across lipid traits, suggesting that the estimates were unstable. In the UK Biobank, there was no evidence of an association between genetically predicted lipid traits and SAH for LDL (HR 1.06 [0.64-1.73]), HDL (HR 2.57 [0.42-15.74]), TC (HR 1.06 [0.71-1.60]), or TG (HR 1.05 [0.69-1.59). Results were consistent across different MR methods and sensitivity analyses, including adjustment for lipid-lowering therapy. Current evidence does not support a major association between lipid traits and SAH, with the heterogeneity observed across previous MR studies likely reflecting methodological limitations rather than a consistent biological effect. However, small effects and lipid-independent effects of lipid-lowering therapies cannot be excluded.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138380","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":"Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Cognitive Outcome after Stroke: A Systematic Review.","authors":"Prach Uthayo, Marc Feldman, Natalie Olivares","doi":"10.1007/s12975-026-01500-2","DOIUrl":"10.1007/s12975-026-01500-2","url":null,"abstract":"<p><p>Post-stroke cognitive impairment (PSCI) is a common and disabling consequence of stroke. Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity, and the BDNF Val66Met (rs6265) polymorphism may alter cognitive outcomes after stroke; however, evidence remains inconsistent. We searched PubMed, Scopus, and Web of Science. Observational studies involving adults with stroke that evaluated the association between BDNF Val66Met and post-stroke cognitive outcomes were included. Two reviewers independently screened studies; one reviewer extracted and another verified the data. Methodological quality was assessed using the Newcastle-Ottawa Scale. Findings were synthesized narratively because of substantial heterogeneity in study population, genotype classification, and cognitive measures. Seven studies involving 2,494 participants met the inclusion criteria. Five studies evaluated global cognitive outcomes. Four reported significant genotype-related associations or differences in global cognition, with three showing poorer cognitive outcomes among Met-allele carriers and one reporting the opposite direction. In the largest cohort, Met carriers had significantly lower 12-month telephone Montreal Cognitive Assessment scores after adjustment for covariates. Memory was the most consistently affected domain, with poorer performance among Met carriers. Evidence for language was inconsistent, while data on attention and executive function were limited. One cohort reported an opposite association, with Val-allele carriers demonstrating poorer global cognition and language performance. One study also identified poorer cognitive functional recovery among Met carriers. BDNF Val66Met may be associated with variability in post-stroke cognitive outcomes, particularly global cognition and memory. However, population-specific findings and methodological heterogeneity preclude definitive conclusions. Larger prospective multicenter studies using standardized cognitive assessments are warranted.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115383","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":"Chemokine CXCL10 and Incident Stroke Risk in the Northern Manhattan Study.","authors":"Mohammad Nafeli Shahrestani, Christian Agudelo, Hannah Gardener, Emir Veledar, Jose A Santiago, Marco R Di Tullio, David Della-Morte, Botagoz Aimagambetova, Jose Gutierrez, Mady Hornig, Mitchell S V Elkind, Hyun Song, Clinton B Wright, Sarah E Tom, Tatjana Rundek","doi":"10.1007/s12975-026-01498-7","DOIUrl":"10.1007/s12975-026-01498-7","url":null,"abstract":"<p><p>Inflammation contributes to cerebrovascular disease, but prospective studies of broad immune marker panels and incident stroke are limited. We aimed to identify plasma immune markers independently associated with incident stroke. Stroke-free Northern Manhattan Study participants aged ≥ 50 years had 60 plasma immune-related proteins measured by Luminex. Least absolute shrinkage and selection operator (LASSO) Cox regression selected markers associated with incident all-cause stroke. Selected markers were tested in Cox models of stroke risk sequentially adjusted for vascular risk, cardiac comorbidities, interleukin-6, interleukin-1β, tumor necrosis factor-α, and white matter hyperintensity volume (WMHV). Ischemic stroke was a secondary outcome, and bootstrap resampling provided internal validation. Among 1175 participants (mean age 70 ± 9 years; 60% women; 67% Hispanic), 130 strokes, 101 (78%) ischemic, occurred over a median of 14 years. LASSO selected only C-X-C motif chemokine ligands 9 and 10 (CXCL9 and CXCL10). Each 1-standard deviation greater CXCL10 was associated with 20% greater all-cause stroke risk after adjustment for vascular risk, cardiac comorbidities, and inflammatory cytokines (HR 1.20; 95%CI 1.04-1.38). The association persisted after WMHV adjustment (HR 1.18; 95%CI 1.02-1.37), was similar for ischemic stroke (HR 1.19; 95%CI 1.01-1.41), and was stable across bootstrap resamples. CXCL9 was not independently associated with stroke. In a multiethnic urban aging cohort followed prospectively for over a decade, baseline plasma CXCL10, also known as interferon-γ-induced protein 10 (IP-10), was independently associated with incident stroke. CXCL10 may mark interferon-γ-responsive immune activity linked to cerebrovascular vulnerability. Whether CXCL10 signals a modifiable pathway for stroke prevention warrants investigation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115341","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":"Exogenous Hydrogen Sulfide Donors Suppress Neointimal Hyperplasia by Modulating Mitochondrial Dysfunction in Vascular Smooth Muscle Cells.","authors":"Yanyan He, Chenqing Li, Bing Zhang, Jia Liang, Chenming Si, Yang Liu, Yu Wang, Chi Ma, Tianxiao Li, Yingkun He","doi":"10.1007/s12975-026-01495-w","DOIUrl":"10.1007/s12975-026-01495-w","url":null,"abstract":"<p><p>Phenotypic switching of vascular smooth muscle cells (VSMCs) from the contractile to the synthetic is a key factor driving the formation of intracranial atherosclerotic stenosis (ICAS); however, the upstream mitochondrial mechanisms underlying this process and its therapeutic implications remain poorly defined. This study aims to investigate the role and underlying molecular mechanisms of the mitochondria-targeted hydrogen sulfide (H₂S) donor AP39 in regulating mitochondrial function during VSMCs phenotypic switching and neointimal hyperplasia. In a platelet-derived growth factor-BB (PDGF-BB)-induced synthetic VSMCs model, mitochondrial function and phenotypic changes were systematically assessed. In vivo, AP39 was locally administered in a mouse carotid artery ligation model to evaluate neointimal formation and vascular remodeling. PDGF-BB induced hypermethylation of the mtDNA D-loop region, ROS accumulation, and Drp1 activation, accompanied by enhanced mitochondrial fission, impaired energy metabolism, and VSMCs phenotypic switching. These alterations were differentially reversed by 5-Aza-dC, NAC, Mdivi-1, or Drp1 silencing. AP39 reduced D-loop methylation and mitochondrial DNMT1 expression, suppressed ROS accumulation and Drp1 activation, preserved mitochondrial structure and oxidative phosphorylation, and attenuated VSMCs phenotypic switching, while partially restoring cystathionine γ-lyase (CSE)-mediated endogenous H₂S production. Consistent with these findings, local AP39 administration in vivo significantly alleviated neointimal hyperplasia following carotid ligation. These results indicate that the mitochondria-targeted H₂S donor AP39 exerts robust vasculoprotective effects through multi-level modulation of D-loop hypermethylation-driven mitochondrial dysfunction, thereby ameliorating ICAS-associated VSMCs phenotypic switching and neointimal hyperplasia. This study provides a novel mechanistic framework and highlights a potential mitochondria-targeted therapeutic strategy for vascular remodeling in ICAS.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064587","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":"Effect Modification of Rescue Stenting in ICAS-Related Middle Cerebral Artery Occlusion: The Role of Thrombectomy Failure, Stenosis Severity, and ASPECTS.","authors":"Andrea M Alexandre, Luca Scarcia, Adam A Dmytriw, Valerio Brunetti, Arturo Consoli, Wen Sun, Yingjie Xu, Xianjun Huang, Joseph D Gabrieli, Charlotte Chung, Alessandro Sgreccia, Mohamad Abdalkader, Yan-Lin Li, Shruthika Kimavath, Mohd Shariq, Giovanni Frisullo, Nicola Limbucci, Francesco Arba, Alessandro Pedicelli, Mauro Gentile, Serena Abruzzese, Mariangela Piano, Maria P Ganimede, Emilio Lozupone, Chiara Gaudino, Riccardo Russo, Julien Burel, Julien Allard, Nicolas Chausson, Roberta Partesano, Nicola Cavasin, Nicolò Mandruzzato, Pietro Trombatore, Antonio A Caragliano, Federico Mazzacane, Giancarlo Salsano, Antioco Sanna, Pietro Panni, Andrea Zini, Frédéric Clarençon, Eytan Raz, Thanh N Nguyen, Aldobrando Broccolini","doi":"10.1007/s12975-026-01496-9","DOIUrl":"10.1007/s12975-026-01496-9","url":null,"abstract":"<p><p>Rescue stenting (RS) is increasingly used for intracranial artery stenosis-related large vessel occlusion (ICAS-LVO), but optimal patient selection remains uncertain. We investigated the baseline and procedural factors associated with receiving RS and whether they modified the association between RS and clinical outcome.This retrospective multicenter study included patients with middle cerebral artery (MCA) ICAS-LVO treated with mechanical thrombectomy (MT) alone or MT followed by RS. Baseline and procedural characteristics associated with receiving RS were identified using multivariable logistic regression and incorporated into inverse probability of treatment weighting models to assess treatment-effect heterogeneity for the 90-day modified Rankin Scale score.Among 264 patients, 193 received RS and 71 MT alone. MT failure, severe stenosis (> 75%), and higher baseline Alberta Stroke Program Early CT Score (ASPECTS) were independently associated with receiving RS. Both MT failure (interaction OR 0.28, 95% CI 0.10-0.83; p for interaction = 0.02) and severe stenosis (interaction OR 0.13, 95% CI 0.03-0.53; p for interaction = 0.004) significantly modified the association between RS and clinical outcome, whereas baseline ASPECTS did not. Within the MT failure subgroup, a significant interaction between severe stenosis and ASPECTS was observed (interaction OR 0.08, 95% CI 0.02-0.38; p for interaction = 0.002), suggesting a more favorable association between RS and outcome at higher ASPECTS values in patients with severe stenosis.In MCA ICAS-LVO, RS may be associated with more favorable outcomes in patients with MT failure, particularly in the presence of severe residual stenosis and preserved ASPECTS. These findings support a more selective approach to RS and warrant prospective validation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026132","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}