Translational Stroke Research最新文献

{"title":"Thrombin Generation Capacity is Associated With Worse Outcome in r-tPA Treated Patients With Stroke.","authors":"Sarina Falcione, Twinkle Joy, Danielle Munsterman, Sushreeta Sai, Roobina Boghozian, Glen Jickling","doi":"10.1007/s12975-026-01490-1","DOIUrl":"10.1007/s12975-026-01490-1","url":null,"abstract":"<p><p>Recombinant tissue plasminogen activator (r-tPA) remains the cornerstone of reperfusion therapy in patients with stroke. However, response to r-tPA is highly variable and not fully explained by clinical factors with many patients not achieving a good outcome despite thrombolysis treatment. In 78 patients with acute ischemic stroke treated with r-tPA, thrombin generation capacity was measured in plasma. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS). In addition, inflammatory markers were analyzed to identify factors associated with increased thrombin generation in this patient population. Thrombin generation capacity was significantly greater in patients with worse 90-day mRS (mRS > 2) compared to those with good 90-day mRS (mRS ≤ 2; 254 nM vs. 210 nM; p = 0.0007). This association remained significant after adjustment for admission NIHSS, age, sex, stroke etiology, and atrial fibrillation (OR: 1.68, 95% CI: 1.10-2.58; p = 0.017). In vitro, increased thrombin was associated with denser fibrin clot structure and prolonged clot lysis time in response to tPA. In patients, peak thrombin levels correlated positively with inflammatory and coagulation markers, including interleukin (IL)-6 (r = 0.421, p = 0.009), IL-8 (r = 0.382, p = 0.018), and fibrinogen (r = 0.415, p = 0.02), and inversely with α2-macroglobulin (α2M; r=-0.327, p = 0.048). Elevated thrombin generation is associated with worse outcomes in patients with acute ischemic stroke treated with r-tPA. This procoagulant state may promote formation of denser, thrombolysis-resistant thrombi and help explain interindividual variability in outcome following treatment. Thrombin generation capacity may serve as a useful biomarker to improve risk stratification and predict variability in thrombolytic response.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851722","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":"Salvaging the No-Reflow Zone: Intra-arterial Cranial Bone-Derived MSCs Restore Neurovascular Integrity After Stroke.","authors":"Takeshi Hara, Masaaki Takeda, Masashi Kuwabara, Yuyo Maeda, Shingo Matsuda, Hiroki Takahashi, Takeshi Imura, Tomoyuki Kurose, Seiji Hama, Takafumi Mitsuhara, Nobutaka Horie","doi":"10.1007/s12975-026-01494-x","DOIUrl":"10.1007/s12975-026-01494-x","url":null,"abstract":"<p><p>Successful macrovascular recanalization does not always translate into functional recovery, in part because early post-reperfusion injury can drive infarct expansion. Here, we investigated whether hyperacute intra-arterial transplantation of human cranial bone-derived mesenchymal stem cells (hcMSCs) immediately after reperfusion improves functional recovery after ischemic stroke. Transient middle cerebral artery occlusion was induced in adult rats, followed by intra-arterial administration of hcMSCs or vehicle immediately after reperfusion. Neurological and motor pathway recovery were assessed longitudinally using the modified neurological severity score and transcranial motor-evoked potentials. During the acute phase, molecular and histological analyses of peri-infarct tissue were performed and the transcriptomic profiles of hcMSCs compared with those of human bone marrow-derived mesenchymal stem cells (hbMSCs). Hyperacute intra-arterial hcMSC transplantation resulted in significantly faster neurological recovery compared with controls, accompanied by enhanced electrophysiological recovery of motor pathway function. These functional improvements were associated with preservation of neuronal structural integrity in the peri-infarct cortex, attenuation of inflammatory cytokines and apoptosis activity, and vascular endothelial growth factor upregulation. Further, transcriptomic analysis revealed that hcMSCs are enriched in neurotrophic, angiogenic, and immunoregulatory factors, providing a biological support for the observed therapeutic effects. Hyperacute intra-arterial hcMSC delivery immediately after reperfusion promotes functional and electrophysiological recovery in an experimental reperfusion model, likely through early modulation of inflammatory and apoptotic responses in the peri-infarct tissue. These findings support further investigation of hcMSC therapy as a biologically protective adjunctive strategy in the immediate post-recanalization setting.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841448","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":"Periodontal Bacteria Proteomics in Thrombi from Ischemic Stroke Patients.","authors":"Florencia Gayo, Susana Bravo, Jorge Moldes, Carmen Pena, Manuel Rodríguez-Yáñez, Rafael Domínguez-Cachón, Ramón Iglesias-Rey, Antonio Jesús Mosqueira-Martínez, Juan Blanco, Tomás Sobrino, Yago Leira","doi":"10.1007/s12975-026-01493-y","DOIUrl":"10.1007/s12975-026-01493-y","url":null,"abstract":"<p><strong>Obejective: </strong>To characterize periodontal bacterial proteins in ischemic stroke thrombi and explore differences according to stroke etiology.</p><p><strong>Methods: </strong>Thrombotic samples were obtained from nine severe periodontal patients with acute ischemic stroke (large-artery atherosclerosis, cardioembolic and undetermined source; 3 patients per stroke subtype) during mechanical thrombectomy. Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Quantitative proteomic profiling was performed by sequential window acquisition of all theoretical mass spectra (SWATH-MS), focusing on proteins from five periodontal bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia, and Treponema denticola. Protein expression was compared across thrombus etiologies, and differentially expressed proteins were further analyzed in silico to explore their functions and interactions.</p><p><strong>Results: </strong>A total of 136 bacterial proteins were quantified, predominantly from A. actinomycetemcomitans (112). Sixteen proteins showed differential expression (p < 0.05), mainly from this species. These were primarily associated with transcription, translation, and stress response mechanisms, including oxidative stress resistance. Few proteins from other species were differentially expressed, mostly related to structural and basic metabolic functions, except for a collagenase from T. forsythia in large-artery atherosclerosis stroke thrombi.</p><p><strong>Conclusions: </strong>SWATH-MS-based proteomic analysis revealed the presence of periodontal bacterial proteins in ischemic stroke thrombi, with a predominance of Aggregatibacter actinomycetemcomitans.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819683","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":"Beyond Acute Kidney Injury : Direct Pathways Implicate Inflammatory Mechanisms in Serum NGAL's Mortality Effect in Acute Brain Injury.","authors":"Hyung Seok Guk, Yong Soo Kim, Dong-Wan Kang, Sang-Hoon Han, Museong Kim, Moon-Ku Han, Kyoungho Suk, Jae-Hong Kim, Han-Gil Jeong","doi":"10.1007/s12975-026-01489-8","DOIUrl":"10.1007/s12975-026-01489-8","url":null,"abstract":"<p><p>Neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in critically ill patients, conventionally attributed to its role in acute kidney injury (AKI) detection. However, NGAL is a neutrophil granule protein released during innate immune activation-a process central to acute brain injury (ABI) pathophysiology. Whether the association between NGAL and mortality in neurocritical care operates through AKI-mediated or alternative pathways has not been evaluated. In this prospective cohort of 274 adults with ABI (98 intracerebral hemorrhage, 60 ischemic stroke, 46 subarachnoid hemorrhage, 70 traumatic brain injury) admitted to a neurocritical care unit, serum NGAL was measured within 24 h of admission. Causal mediation analysis with time-varying AKI status decomposed NGAL's mortality effect into direct and AKI-mediated components. High NGAL (≥ 150 ng/mL) was independently associated with in-hospital mortality (adjusted hazard ratio [aHR] 2.94, 95% confidence interval [CI] 1.57-5.51; absolute risk difference 15.0% at 28 days), ICU mortality, 6-month mortality, and worse functional outcomes. Pathway decomposition revealed a significant direct effect not mediated through AKI (aHR 2.15, 95% CI 1.04-4.62, P=.04), whereas the AKI-mediated component was not significant (P=.33). Effects were consistent across injury types. Admission NGAL correlated with subsequent 72-hour systemic inflammatory burden (Spearman ρ = 0.38, P<.001), and within-subject NGAL and interleukin-6 showed concordant temporal trajectories (repeated-measures r = .29, P<.001). These findings indicate that the NGAL-mortality association in ABI includes a significant direct effect not mediated through AKI, implying that NGAL elevation reflects systemic innate immune activation rather than impending renal dysfunction.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814059","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":"Microglial Immunometabolic Remodeling After Ischemic Stroke: The Interplay Between Mitochondrial Stress and the Ischemic Microenvironment.","authors":"Cui Liu, Qiang Liu, Weiyao Jing, Limei Liu, Long Wei, Xing Li, Xiaozheng Du","doi":"10.1007/s12975-026-01492-z","DOIUrl":"10.1007/s12975-026-01492-z","url":null,"abstract":"<p><p>Following ischemic stroke, marked alterations in the local metabolic and inflammatory milieu of the brain drive immunometabolic remodeling and mitochondrial dysfunction in microglia, thereby shaping inflammation, damage clearance, and tissue repair. Existing studies have largely focused on individual metabolic pathways, leaving the relationships among the ischemic microenvironment, mitochondrial responses, and microglial functional changes incompletely understood. Available evidence indicates that the effects of these metabolic alterations vary with stroke phase, local injury severity, and mitochondrial status. This review summarizes current evidence on glycolysis and lactate transport, the tricarboxylic acid cycle and succinate signaling, lipid handling, and danger-signal sensing, with particular emphasis on their relationships with mitochondrial redox homeostasis and quality control. We also critically evaluate divergent findings across studies. By examining the interaction between the ischemic microenvironment and mitochondrial responses, this review aims to clarify the metabolic basis of microglial functional changes and to inform the assessment of potential therapeutic targets in microglial immunometabolism.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798393","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":"Therapeutic Potential of NLRP3 Inhibitor MCC950 in Aging Mice Stroke Outcomes.","authors":"Pradip K Kamat, Mohammad Badruzzaman Khan, Shahneela Siddiqui, Ashraar Dua Dua, Sanvi Divekar, Heidi David, Mohammad A Hussain, Sanket Gavankar, David C Hess","doi":"10.1007/s12975-026-01491-0","DOIUrl":"10.1007/s12975-026-01491-0","url":null,"abstract":"<p><p>The inflammatory cascade worsens tissue injury and clinical outcomes in acute stroke. The NLRP3 inflammasome plays a central role in the innate immune system. Aged humans and mice exhibit chronic sterile inflammation, known as \"inflammaging,\" characterized by activation of the innate immune system. Our central hypothesis is that inhibiting the NLRP3 inflammasome will improve long-term functional outcomes in aged mice subjected to middle cerebral artery occlusion. We aimed to investigate the long- and short-term effects of MCC950, an NLRP3- specific inhibitor, on stroke outcomes. In this study, 14-15-month-old C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) under isoflurane anesthesia. Mice were treated with MCC950 (50 mg/kg, first day and then 10 mg/kg per day) or vehicle (i.p) up to 72 h in the short-term experiment. A 10 mg/kg (i.p) daily or vehicle for 28 days (5x/week) in the long-term experiment were given. Behavioral studies were performed at the end of each experimental set using the corner test, beam walk, hanging wire, Y maze, NOR test, and a battery of neurobehavioral tests. The mice were sacrificed, and the whole brain tissue was used to assess IL-1β, IL-18, TNFα, NLRP3, Caspase 1, and GSDMD expression by qPCR. NLRP3, Caspase 1, IL1β, IL18, Claudin5, occludin, Zona occludin (ZO1), and GSDMD were also estimated by Western blot assay. Histopathology was performed to assess the neuronal damage and white matter loss. MCC950 treatment in aging stroke mice attenuated inflammatory changes, BBB impairment, and rescued stroke-induced neurobehavioral impairment in acute as well as in chronic treatment. The infarction area was reduced in the short-term experiment. Our study suggests that MCC950 is a promising therapy for acute stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798334","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":"Roles of Ceramide Glucosyltransferase in Controlling Cerebral Microvascular Endothelial Integrity and Angiogenesis Post-Ischemia/Reperfusion.","authors":"Ayan Mohamud Yusuf, Maria Zafar, Nina Hagemann, Ulf Brockmeier, Fabian Schumacher, Burkhard Kleuser, Tobias Tertel, Bernd Giebel, Erich Gulbins, Dirk M Hermann","doi":"10.1007/s12975-026-01488-9","DOIUrl":"10.1007/s12975-026-01488-9","url":null,"abstract":"<p><p>Sphingolipids critically regulate microvascular integrity and function, but the role of glycosphingolipids in endothelial survival and angiogenesis remains poorly defined. Herein, we experimentally deactivated or activated UDP-glucose ceramide glucosyltransferase (UGCG), which converts ceramide to glucosylceramide, by the pharmacological inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), siRNA-mediated knockdown or the pharmacological activator L-PDMP. Sphingolipid and glycosphingolipid profiles were examined by liquid chromatography-tandem-mass spectrometry. Effects on endothelial survival, proliferation, transwell migration, extracellular vesicle (EV) release and tube formation were assessed in human cerebral microvascular endothelial cells (hCMEC/D3). In vitro, pharmacological UGCG deactivation near-completely suppressed hexosylceramide levels and at high dose increased ceramide and sphingosine-1-phosphate (S1P), a known pro-angiogenic sphingolipid, while UGCG knockdown moderately decreased mostly short (C16, C18) hexosylceramides. UGCG activation increased hexosylceramide without significantly altering ceramide and S1P. Pharmacological UGCG deactivation increased endothelial tube formation, a marker of angiogenesis, but at high dose decreased endothelial survival, whereas UGCG knockdown and UGCG activation reduced endothelial tube formation and migration or proliferation, respectively. Pharmacological UGCG deactivation and activation, but not UGCG knockdown increased endothelial release of EVs with anti-angiogenic activity. In mice exposed to transient middle cerebral artery occlusion, pharmacological UGCG deactivation and activation reduced the length and branch density of small-sized (< 4 µm) and intermediate (4-5.4 µm) cerebral microvessels in the reperfused striatum as revealed by 3D light-sheet microscopy, indicative of microvascular endothelial degeneration. Our results suggest that pharmacological UGCG deactivation promotes angiogenesis in vitro probably via S1P elevation. In vivo, UGCG deactivation failed to stabilize microvascular network integrity post-ischemia/reperfusion, presumably due to ceramide-associated cell stress.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798416","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":"Astrocyte-Microglia Crosstalk in Post-Hemorrhagic Neurovascular Microenvironment: Mechanistic Nodes, Cross-Stroke Comparisons, and Therapeutic Reprogramming.","authors":"Feng Ye, Ruilian Chen, Shicai Xu, Hao Liu, Jianguo Xu","doi":"10.1007/s12975-026-01478-x","DOIUrl":"10.1007/s12975-026-01478-x","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) produces a rapidly evolving and spatially heterogeneous neurovascular microenvironment in which secondary injury is shaped not only by hematoma volume and location, but also by the interaction of blood-derived toxins, blood-brain barrier disruption, edema, oxidative stress, protease activity, and glial responses. Increasing evidence suggests that these processes are better understood as dynamic network events rather than isolated inflammatory pathways.</p><p><strong>Main body: </strong>This review applies a network-centered framework to astrocyte-microglia coupling, viewing it as a critical control layer that may either support injury containment and hematoma resolution or drive persistent neurotoxicity and failed repair. Comparisons with ischemic stroke are used to distinguish shared inflammatory modules from hemorrhage-specific drivers, including heme, hemoglobin, iron overload, thrombin, fibrinogen, and clot-associated protease signaling. Integrating findings from single-cell and spatially resolved studies, the review summarizes the temporal and spatial organization of post-hemorrhagic microenvironment remodeling and discusses astrocyte-dependent regulation of barrier function, edema dynamics, immunometabolism, redox buffering, and synaptic homeostasis. It also examines how astrocyte-derived cues influence microglial state transitions through danger sensing, inflammasome signaling, cyclic GMP-AMP synthase-stimulator of interferon (IFN) genes signaling, phagocytic containment, iron-handling programs, complement-mediated synaptic vulnerability, and interaction with infiltrating myeloid cells. Recurring astrocyte-microglia network motifs are further evaluated as therapeutic control points, with emphasis on how lesion stage and spatial compartmentalization shape intervention windows for purinergic, chemokine, cytokine, IFN, complement-coagulation, and lipid/iron signaling pathways. Translational priorities, limitations, and therapeutic opportunities are discussed across hematoma-toxicity reduction, barrier and edema repair, network reprogramming, and regenerative microenvironment shaping.</p><p><strong>Conclusion: </strong>Meaningful improvement in ICH outcome will likely depend on biomarker-guided and stage-specific reprogramming of astrocyte-microglia network dynamics to restore microenvironmental balance, rather than on nonspecific suppression of neuroinflammation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707835","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":"From Recanalization to Failed Recovery: No Reflow, No Rescue, and No Regrow After Thrombectomy.","authors":"Ariana Chacon, Dareen Hijazi, Ali Tfaily, Brian M Howard, Stephen Tomlinson, Jonathan A Grossberg, Ali M Alawieh","doi":"10.1007/s12975-026-01487-w","DOIUrl":"10.1007/s12975-026-01487-w","url":null,"abstract":"<p><p>Despite the remarkable technical success of endovascular thrombectomy (EVT) in achieving high recanalization rates for acute ischemic stroke due to large vessel occlusion (LVO), angiographic success does not consistently translate into functional recovery. Approximately 50% of successfully recanalized patients failed to achieve functional independence at 90 days, a phenomenon termed futile recanalization (FR). Futile recanalization highlights the biological limitations of macrovascular reperfusion alone. We propose a mechanistic framework for FR centered on the \"3 R's\" of stroke recovery: No-Reflow, No-Rescue, and No-Regrow. No-Reflow refers to microvascular failure despite proximal recanalization, driven by capillary obstruction, endothelial injury, pericyte constriction, and thromboinflammatory processes. No-Rescue describes secondary loss of initially salvageable neurons due to complement activation, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction. No-Regrow reflects impaired neuroplasticity in the subacute and chronic phases, including failed neurogenesis, axonal degeneration, white matter injury, and disrupted network reorganization. This review examines the clinical, imaging, procedural, and molecular determinants of FR to better understand why successful reperfusion does not always result in neurological recovery. Understanding the multifactorial nature of FR is essential to improving EVT outcomes. Future strategies should target microvascular injury and inflammation, refine patient selection criteria, and explore adjunctive therapies aimed at restoring downstream perfusion and mitigating neuroinflammation. By addressing both macrovascular and microvascular factors, it may be possible to translate angiographic success into meaningful functional recovery.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685818","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":"Association of Traditional and Novel Lipid Indicators With the Hemorrhagic Phenotype in Adult Moyamoya Disease: Implications for Phenotype Stratification.","authors":"Weihong Huang, Haoyang Xiong, Wenjing Chen, Wei Liu, Peicong Ge, Yunhao Liu, Xuefeng Tang, Ziheng Yang, Zhongji Yan, Dong Zhang","doi":"10.1007/s12975-026-01486-x","DOIUrl":"10.1007/s12975-026-01486-x","url":null,"abstract":"<p><p>To investigate the associations of traditional and novel lipid parameters with the hemorrhagic phenotype in adults with primary moyamoya disease (MMD) and to evaluate their value for phenotype discrimination and stratification. This retrospective dual-center cross-sectional study included 1,176 adults with primary MMD treated at Beijing Hospital and Beijing Tiantan Hospital between January 2022 and January 2026, including 857 patients with a non-hemorrhagic phenotype and 319 with a hemorrhagic phenotype. Traditional and derived lipid parameters were analyzed. Missing body mass index values were handled using multiple imputation. Multivariable logistic regression, restricted cubic spline analysis, receiver operating characteristic analysis, incremental discrimination analysis, sensitivity analyses, subgroup analyses, and exploratory mediation analysis were performed. Compared with patients with the non-hemorrhagic phenotype, those with the hemorrhagic phenotype had lower body mass index and higher levels of several cholesterol-related lipid parameters. In fully adjusted models, total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol were significantly associated with the hemorrhagic phenotype, with odds ratios for the highest versus lowest quartile of 3.435, 3.197, and 3.150, respectively. These indicators showed modest individual discriminative ability and provided limited incremental improvement when added to the basic clinical model. Sensitivity and subgroup analyses were generally consistent. Exploratory analyses identified BMI-related negative indirect effects. Cholesterol-related lipid parameters, particularly total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, were associated with the hemorrhagic phenotype in adult primary MMD and may serve as supplementary markers for phenotype stratification.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685766","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}