Translational Stroke Research最新文献

{"title":"Circulating Microglia-derived Extracellular Vesicles Predict Recovery After Rehabilitation in Stroke Survivors.","authors":"Aurora Mangolini, Silvia Picciolini, Pietro Arcuri, Donata Bardi, Leandro Cosco, Francesca Cecchi, Lorenzo Romagnoli, Ester Marra, Pietro Parisse, Andrea Mannini, Jorge S Navarro, Marzia Bedoni, Alice Gualerzi","doi":"10.1007/s12975-026-01433-w","DOIUrl":"10.1007/s12975-026-01433-w","url":null,"abstract":"<p><p>Timely intensive rehabilitation is crucial to contrast the negative escalation of events that follow a stroke injury, to promote tissue regeneration, and to restore the physiological function. This study aimed to identify measurable blood biomarkers that could be predictive of functional recovery in stroke survivors. 30 sub-acute stroke subjects were enrolled at Fondazione Don Gnocchi (Italy) during the observation prospective study EXO4STROKE (NCT05370105). Following clinical assessment, cytokines, neurofilaments and circulating Extracellular Vesicles (EVs) were evaluated in the serum of patients at admission (T0) and at discharge (T1) in intensive rehabilitation unit. Multiplexed SPRi analysis of circulating EVs allowed detection of brain (neurons, astrocytes, microglia) and non-brain (endothelium, skeletal muscle, and platelets) derived EVs, and the relative quantification of markers of pathological or regenerative processes. Machine learning-based analysis complemented the study by integrating statistically significant features in a cross-validated prediction model targeting functional recovery at T1 from T0 data. The results of the present study demonstrate that high serum levels of IL-6 and Neurofilament Light Chain at T0 were associated with higher residual disability at T1. In contrast, elevated circulating levels of EVs from neurons (CD171+) and microglia (CD11b+) were associated with better recovery after rehabilitation. Moreover, the overexpression of the VEGF receptor on microglial EVs was associated with higher functional improvement. Alternatively, the overexpression of TGF-β receptor on IB4 + EVs post-stroke was found associated with increased stroke severity. In conclusion, this study identifies a panel of few circulating biomarkers able to objectively assess post-stroke status and potentially predict functional recovery after rehabilitation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781987","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":"Impaired Glymphatic-Meningeal Lymphatic Function in Patients with Spontaneous Subarachnoid Hemorrhage.","authors":"Jianan Lu, Miao Lin, Heping Tian, Yibo Liu, Bingrui Zhu, Jin Mao, Jiahao Zhang, Haocheng Zhang, Sixuan Tian, Xu Li, Ding Xu, Chenhan Ling, Jianru Li, Hui Hong, Peiyu Huang, Jianmin Zhang, Chao Wang, Sheng Chen, Yuanjian Fang","doi":"10.1007/s12975-026-01438-5","DOIUrl":"10.1007/s12975-026-01438-5","url":null,"abstract":"<p><p>According to animal studies, glymphatic–meningeal lymphatic dysfunction contributes to poor prognosis and the development of chronic hydrocephalus after subarachnoid hemorrhage (SAH). This study aimed to evaluate glymphatic function and meningeal lymphatic drainage signal in patients with SAH. SAH patients and healthy controls (HCs) were enrolled and underwent multimodal MRI. Glymphatic function was assessed using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, free water in white matter (FW-WM), and white matter perivascular space volume fraction (PVSVF-WM). The signal intensity (SI) of meningeal lymphatic vessels (mLVs) and deep cervical lymph nodes (dcLNs) was also quantified as an imaging surrogate of meningeal lymphatic drainage. Compared with HCs, SAH patients exhibited significant impairment of glymphatic function, characterized by a reduced DTI-ALPS index, increased FW-WM, and increased PVSVF-WM, along with reduced SI of the mLVs and dcLNs. Patients with chronic hydrocephalus showed even more pronounced impairment than those with acute SAH. Importantly, reduced DTI-ALPS index and mLV SI loss were identified as independent predictors of chronic shunt-dependent hydrocephalus. Notably, 53.8% of chronic hydrocephalus patients exhibited fluid accumulation in the mastoid air cells, inversely correlated with meningeal lymphatic drainage signal. In conclusion, SAH is associated with acute and persistent impairment of glymphatic function and reduced meningeal lymphatic drainage signal, with early MRI-derived metrics serving as potential predictors of chronic hydrocephalus and poor functional outcomes.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781971","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":"Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.","authors":"Takahiro Tsuchiya, Satoru Miyawaki, Hideaki Ono, Hiroki Hongo, Shotaro Ogawa, Yu Sakai, Yudai Hirano, Daisuke Sato, So Hirata, Satoshi Koizumi, Nobuhito Saito","doi":"10.1007/s12975-026-01436-7","DOIUrl":"10.1007/s12975-026-01436-7","url":null,"abstract":"<p><p>Brain arteriovenous malformations (bAVMs) are high-flow vascular lesions characterized by direct arteriovenous shunting without an intervening capillary bed. The identification of somatic KRAS and BRAF mutations in sporadic bAVM endothelial cells (ECs) has fundamentally reshaped current understanding of bAVM biology, indicating that activation of the RAS/MAPK pathway drives aberrant angiogenic programs. In parallel, advances in genomic technologies have led to recognition of bAVMs as dynamic lesions that undergo ongoing vascular remodeling. Comprehensive transcriptomic profiling, including single-cell RNA sequencing, has uncovered distinctive molecular signatures in bAVM ECs, including heightened angiogenic and inflammatory signaling, endothelial-to-mesenchymal transition–like features, and loss of normal arteriovenous identity. Furthermore, animal models with EC-specific expression of mutant KRAS or BRAF exhibit bAVM-like lesions, which support the hypothesis that hyperactivation of the RAS/MAPK pathway is a key driver of lesion formation. These insights have accelerated the development of mechanism-based therapeutic strategies, and MEK and BRAF inhibitors targeting the RAS/MAPK pathway have shown promising results in preclinical studies. However, clinical translation remains challenging because of low variant allele frequencies and limited access to lesional tissue for genetic testing. Future approaches combining minimally invasive sampling methods, such as endovascular biopsy and peripheral blood cell-free DNA analysis, with ultra-sensitive detection technologies are expected to help overcome these limitations. Taken together, accumulating genetic evidence and a growing understanding of the inflammatory and immune microenvironment provide an important foundation not only for a deeper understanding of bAVM pathobiology but also for the development of future targeted therapies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717883","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":"Cytotoxic Edema and Intra-parenchymal Hemorrhage: A Mediated Pathway to Mortality and Functional Outcome in Cerebral Venous Sinus Thrombosis- A sub-analysis of the CLOT-VENUS Registry.","authors":"Nashwa Abdelhakim, Milagros Galecio-Castillo, Piyush Kalakoti, Leonardo Cruz-Criollo, Aaron Rodriguez-Calienes, Anderson Brito, Jorge Cespedes, Amir Shaban, Anish Venkatesan, Vanessa Cano Nigenda, Andres Alberto Mercado Pompa, Nicholas M Mohr, Adrian Pereda-Castillo, Kevin Enríquez Peregrino, Hector Valdez Ruvalcaba, Brian J Smith, James C Torner, Miguel A Barboza, Antonio Arauz, Santiago Ortega-Gutierrez","doi":"10.1007/s12975-026-01426-9","DOIUrl":"10.1007/s12975-026-01426-9","url":null,"abstract":"<p><p>Cytotoxic edema (CE) is a radiographic marker of early tissue injury in cerebral venous thrombosis (CVT) associated with poor outcomes, yet its mechanistic pathway remains unclear. We investigated whether intraparenchymal hemorrhage (IPH) mediates the association between CE and outcomes. We conducted a retrospective cohort study using the multicenter CLOT-VENUS registry, including acute CVT patients treated at two Comprehensive Stroke Centers in the USA and Mexico (2004-2024). CE was defined as hyperintensities around IPH or venous infarct with DWI restricted diffusion and corresponding low ADC, confirming true restricted diffusion. IPH was defined as hemorrhagic transformation of venous infarction or intracerebral hemorrhage on GRE MRI and/or NCCT. Mediation analyses assessed whether IPH mediated CE associations with in-hospital mortality and functional outcomes. Among 394 patients (mean age 42.7 years; 65.5% female), 128 (32.5%) demonstrated CE and 111(30.2%) IPH. CE was associated with in-hospital mortality (aOR 2.63, 95% CI 1.01-7.12) and poor 6-month mRS (aOR 1.71, 95% CI 1.06-2.74). CE was associated with IPH, which in turn was associated with mortality (aOR 8.73, 95% CI 2.93-30.45) and poor mRS (aOR 1.96, 95% CI 1.18-3.25). Adjustment for IPH rendered the CE-outcome associations non-significant. IPH accounted for 76.8% of CE's effect on mortality and 83.8% on 6-month mRS. Our findings suggest that IPH likely mediates the effect of CE on outcomes in CVT. Although the temporal sequence could not be confirmed, the results underscore the value of early CE detection for timely intervention.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677023","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":"A Deep-Learning Model for Stroke Subtype Identification in Moyamoya Disease Based on Digital Subtraction Angiography.","authors":"Zhi-Wen Liu, Fei Shang, Ri-Miao Yang, Cong Han, Shuai Liu, Guo-Zheng Xu","doi":"10.1007/s12975-026-01432-x","DOIUrl":"10.1007/s12975-026-01432-x","url":null,"abstract":"<p><p>Moyamoya disease (MMD) may present with ischemic or hemorrhagic stroke, with differing prognosis and management. Early identification of the likely stroke subtype could support individualized therapeutic planning. We developed an interpretable digital subtraction angiography (DSA)–based deep-learning model to classify stroke subtype in adult MMD. This retrospective study included 163 adults with MMD (98 ischemic, 65 hemorrhagic) who underwent DSA between January and December 2016. Images from predefined vessels and projection planes were preprocessed and augmented. Convolutional neural network (CNN) classifiers were trained using single-vessel images and combined-vessel images. Data were split into a training set (80%, n = 130) and an independent test set (20%, n = 33). Model interpretability was assessed using gradient-weighted class activation mapping (Grad-CAM++). Baseline characteristics were comparable between the training and test sets. Among single-vessel models, sagittal vertebral artery (VA) images achieved the best performance (F1 = 0.929; accuracy = 0.939), comparable to sagittal external carotid artery (ECA) images. For the same vessel, sagittal projections consistently outperformed coronal views. A combined model incorporating sagittal internal carotid artery (ICA) and sagittal VA images also achieved optimal performance (F1 = 0.929; accuracy = 0.939). Grad-CAM + + highlighted discriminative regions along the ICA and VA, consistent with clinical assessment. A DSA-based CNN can accurately distinguish ischemic versus hemorrhagic presentation in adult MMD. Posterior circulation features—particularly the VA—and sagittal projections provide strong predictive signal, supporting the translational relevance of posterior circulation morphology for hemorrhagic MMD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677035","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":"Non-Linear Temporal Dynamics of Endothelial Progenitor Cells After Stroke: Associations with Perfusion Imaging, ASPECTs and Functional Outcome.","authors":"Juan Francisco García Granado, Francisco Javier Rodríguez Esparragón, Ernesto Santana Suárez, Jesús María González Martín, Sara Estefanía Cazorla Rivero, Almudena Raposo Usero, Ayoze Nauzet González Hernández","doi":"10.1007/s12975-026-01431-y","DOIUrl":"10.1007/s12975-026-01431-y","url":null,"abstract":"<p><p>Endothelial progenitor cells contribute to neurovascular repair after stroke. This study evaluated their temporal dynamics, prognostic value, and association with neuroimaging markers in stroke patients. We conducted a prospective cohort of 114 patients with ischemic strokes admitted to Hospital Universitario de Gran Canaria Doctor Negrín (Spain) between September 2023 and June 2024. EPC counts were measured at 48 h, 7 days, and 3 months and correlated with 3-month functional outcome (modified Rankin Scale, mRS). Neuroimaging included non-contrast CT (ASPECTS, established infarction) and, in a subgroup (n = 8), perfusion CT (ischemic core, hypoperfusion, Tmax > 10s, and related indices). The primary objective was to evaluate the association between EPC levels at 7 days and functional outcome at 3 months. Secondary objectives included characterization of EPC temporal dynamics and their association with neuroimaging markers, including non-contrast CT and exploratory CT perfusion parameters. EPC levels exhibited a non-linear temporal trajectory over time (ANOVA quadratic trend, p = 0.011; linear mixed model [LMM], p < 0.001), with LMM showing exploratory stroke subtype–specific dynamics (p = 0.006). Pairwise Wilcoxon analyses showed a significant decrease in EPC counts from 48 h to 7 days (p = 0.018), with no statistically significant differences between 7 days and 3 months or between 48 h and 3 months. EPC levels at 7 days demonstrated a modest but statistically significant discriminative ability for 3-month functional outcome (AUC = 0.623, p = 0.036). EPC counts were not associated with ASPECTS or established infarction. In exploratory perfusion analyses, EPC levels at 7 days were significantly correlated with absolute perfusion volumes, including ischemic core, hypoperfusion volume, and tissue with Tmax > 10 s, whereas relative perfusion indices showed no significant associations. EPC counts display a non-linear temporal evolution after ischemic stroke and show a modest association with functional outcome at 3 months. EPC mobilization appears more closely related to the absolute burden of ischemic injury than to relative perfusion indices. Although limited as standalone biomarkers, EPC measurements may contribute to multimodal prognostic assessment when integrated with clinical and imaging data.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623592","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":"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/s12975-026-01430-z","DOIUrl":"10.1007/s12975-026-01430-z","url":null,"abstract":"<p><p>This study investigated the variation characteristics of static fractional amplitude of low-frequency fluctuations (sfALFF) and dynamic fALFF (dfALFF) in Middle cerebral artery stenosis or occlusion(MCA-S) patients, and explored these two indicators alterations with cerebrovascular reactivity (CVR) correction. A total of 41 MCA-S patients and 50 matched controls underwent resting-state functional MRI and neuropsychological testing. Group differences in sfALFF/dfALFF were compared between the two groups, and the brain regions with differences in sfALFF/dfALFF with and without CVR correction were explored. Subsequently, partial correlation analysis was employed to evaluate the correlation between the abnormal brain regions and neuropsychological assessments. After CVR correction, MCA-S patients displayed increased sfALFF in Vermis_6, ipsilesional Cerebelum_8, Hippocampus, and other regions, alongside elevated dfALFF in Vermis_7, ipsilesional Hippocampus, and contralesional Cerebelum_8 (P < 0.001). No significant correlations were found between fALFF metrics and neuropsychological scores post-Bonferroni correction. Uncorrected analyses showed group differences in sfALFF/CVR within ipsilesional Occipital_Mid and Parietal_Inf, while CVR-adjusted results revealed changes in ipsilesional Cerebelum_8 and contralesional Caudate (P < 0.05). For dfALFF, uncorrected differences emerged in ipsilesional Postcentral, whereas CVR correction highlighted ipsilesional Temporal_Inf alterations. In summary, MCA-S patients exhibited abnormal neuronal activity associated with both sfALFF and dfALFF. With CVR correction, vascular confounding effects on the BOLD signal were partially mitigated, thereby enabling more accurate reflection of underlying neural activity alterations.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594947","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":"A Segatella Copri-centered Gut Microbiota-mediated Metabolic Dysregulation Associated with Transition from Asymptomatic to Symptomatic Intracranial Atherosclerosis.","authors":"Manqi Zheng, Xiao Yang, Ruobing Tian, Xue Xia, Qin Xu, Ying Hui, Shuohua Chen, Yan Liu, Anxin Wang","doi":"10.1007/s12975-026-01428-7","DOIUrl":"10.1007/s12975-026-01428-7","url":null,"abstract":"<p><p>The mechanisms underlying the continuum from asymptomatic intracranial atherosclerotic stenosis (aICAS) to symptomatic intracranial large-artery atherosclerotic ischemic stroke (iLAA-IS) remain unclear. We investigated the gut microbiota-metabolite axis in this transition to identify predictive biomarkers and clarify key functional pathways. In a case-control study (63 iLAA-IS cases; 56 aICAS controls), fecal shotgun metagenomics and untargeted plasma metabolomics were profiled. Using machine learning with 10-fold nested cross-validation, we identified five robust biomarkers associated with the transition: Alistipes putredinis (risk-associated) and four protective features (Segatella copri, Gln-Gly, Methionine Sulfoxide, and N6-Acetyl-L-Lysine). Integrated models incorporating these markers significantly improved predictive performance relative to conventional risk factors (e.g., mean AUC of Gln-Gly: 0.9104 vs. 0.7188). Mechanistic analyses revealed a Segatella copri-centered metabolic dysregulation: its depletion coincided with a broad loss of anabolic pathways (BCAA biosynthesis, folate-SAM-methionine metabolism, and tRNA charging), which were positively linked to amino acid-related metabolites. In contrast, the pathways of Alistipes putredinis showed no such coupling. These findings suggest that the aICAS-to-iLAA-IS transition is characterized by chronic metabolic dysregulation, involving a Segatella copri-centered microbiota-metabolite axis. This multi-omic signature offers novel insights into stroke pathogenesis and potential targets for prevention.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147533005","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":"Cerebral Small Vessel Disease and Blood-Brain Barrier Disruption: Mechanisms and Therapeutic Strategies in Cognitive Impairment.","authors":"Yang Yang, Yuhang Qian, Jun Huang, Ying Luo","doi":"10.1007/s12975-026-01427-8","DOIUrl":"10.1007/s12975-026-01427-8","url":null,"abstract":"<p><p>To evaluate the molecular and cellular mechanisms underlying cerebral small vessel disease (CSVD) pathophysiology, the blood-brain barrier (BBB) dysfunction, and emerging therapeutic strategies for cognitive impairment. We conducted a comprehensive review of recent literature examining the relationship between CSVD and BBB disruption, focusing on pathophysiological mechanisms and therapeutic approaches. Key databases were searched for relevant studies investigating inflammatory responses, lipid metabolism, endothelial dysfunction, and their impact on cognitive function in CSVD. BBB disruption plays a central role in CSVD pathogenesis, characterized by increased permeability that triggers neuroinflammatory cascades and subsequent cognitive deterioration. Neuroinflammation, oxidative stress, and disrupted lipid metabolism synergistically contribute to BBB breakdown, creating a detrimental feedback loop. Therapeutic strategies targeting these pathways, including vascular risk factor management, anti-inflammatory interventions, and non-pharmacological approaches such as cognitive training and physical exercise, show promising results in preserving cognitive function in CSVD patients. This review provides critical insights into the complex interplay between CSVD and BBB integrity, emphasizing BBB disruption as both a consequence and amplifier of CSVD-related pathology. Understanding these mechanisms offers novel perspectives for developing targeted interventions to mitigate cognitive decline in affected individuals and addresses a significant public health challenge in our aging global population. We also integrate recent evidence connecting BBB leakage to lipid dysmetabolism, EndMT, and impaired perivascular clearance, and propose a BBB-centered framework for CSVD-related cognitive impairment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522114","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":"Phenotype-Aligned Metabolomics Identifies Plasma Arginine as a Candidate Predictor of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.","authors":"Krzysztof Urbanowicz, Karol Wiśniewski, Mikołaj Opiełka, Michał Bieńkowski, Marta Popęda, Oliwier Krajewski, Ernest J Bobeff, Karol Zaczkowski, Bartosz Szmyd, Dariusz J Jaskólski, Ryszard T Smoleński","doi":"10.1007/s12975-026-01421-0","DOIUrl":"10.1007/s12975-026-01421-0","url":null,"abstract":"<p><p>Delayed cerebral ischemia (DCI) affects approximately 30% of aneurysmal subarachnoid hemorrhage (aSAH) survivors and is a leading cause of morbidity and mortality post-aSAH. Current risk assessment relies on radiographic severity scores that stratify populations based on hemorrhage characteristics but cannot predict DCI onset for individual patients. No plasma-based biomarkers for DCI prediction currently exist. We used liquid chromatography – mass spectrometry to perform plasma metabolomics in 60 aSAH patients (50% female, 30 DCI, 30 No-DCI) with longitudinal sampling until 7 days post-aSAH. Samples were retrospectively aligned to individual DCI onset times per patient, isolating 24–48 h and 48–72 h pre-event windows. Arginine emerged as the sole FDR-significant metabolite 24–48 h before DCI (q = 0.022, 39% depletion) and ranked #1 of 2,022 metabolites across three statistical methods (Student’s t-test, Welch’s t-test, Mann-Whitney U test, p = 10⁻⁵ to 10⁻⁴). Zero metabolites achieved FDR significance at 48–72 h, confirming temporal specificity. Independent logistic regression validated predictive performance (odds ratio 0.22, p = 0.001, AUC 0.808, 95% CI: 0.647–0.945), outperforming modified Fisher radiographic score (AUC 0.718, 95% CI: 0.593–0.830). The combination model of arginine and modified Fisher score performed best with AUC 0.856 (95% CI: 0.733–0.955), with arginine as the dominant factor. Mechanistic investigation revealed FDR-significant depletion of arginine/ornithine (q = 0.011) and glutamine/glutamate ratios (q = 0.011), consistent with increased arginase activity competing with nitric oxide synthesis. Plasma arginine represents a candidate single-molecule biomarker for DCI with a clinically actionable pre-event detection window, pending prospective validation. Temporal alignment to individual DCI onsets enabled detection of pre-event metabolic changes 24–48 h before symptom onset.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515048","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}