Translational Stroke Research最新文献

{"title":"The Impact of VEGFA rs2010963 on Bilaterality and Posterior Artery Stenosis in Patients with Moyamoya Disease.","authors":"Akikazu Nakamura, Hiroyuki Akagawa, Koji Yamaguchi, Kenko Azuma, Taichi Ishiguro, Takahiro Hori, Shuhei Morita, Yasuo Aihara, Sandra Vetiska, Ann Mansur, Ivan Radovanovic, Akitsugu Kawashima, Takakazu Kawamata, Shunsuke Nomura","doi":"10.1007/s12975-026-01484-z","DOIUrl":"10.1007/s12975-026-01484-z","url":null,"abstract":"<p><p>VEGFA plays a pivotal role in angiogenesis and is known to affect clinical phenotypes related to the vasculature in various diseases, such as cancer or stroke. However, it is still unclear how the VEGFA genotype influences the clinical phenotype of moyamoya disease (MMD). This study included 137 Japanese MMD patients (84 adult and 53 pediatric patients) carrying either the heterozygous RNF213 p.R4810K or the RNF213 wild-type genotypes. Patients with homozygous RNF213 p.R4810K genotype or the other rare RNF213 variants were excluded because these genotypes are already known to affect the clinical phenotype. After genotyping VEGFA rs2010963 (NM_001171623.2, c.-634G > C, also known as c.+405G > C), we statistically analyzed the genotype-phenotype correlation. Genotyping and clinical data collection were both blinded. 110 (80.3%) patients carried the heterozygous RNF213 p.R4810K genotype. For VEGFA rs2010963 genotypes, 36 (26.3%) patients had the G/G genotype, 86 (62.8%) had the C/G genotype, and 15 (10.9%) had the C/C genotype. In the subgroup analysis, the VEGFA rs2010963 C/G + C/C genotype was significantly associated with a higher incidence of bilaterality and PCA involvement in pediatric MMD patients (p = 0.032 and 0.0399, respectively). Furthermore, a multivariate regression analysis confirmed the significant association for them (p = 0.0391 and 0.0271, respectively). This genotype-phenotype association study suggests that the VEGFA rs2010963 CG + CC genotype may be associated with a higher rate of bilaterality and PCA stenosis in pediatric MMD patients, in addition to the well-known association of RNF213. These findings suggest that both RNF213 and VEGFA genotypes may be useful in the clinical assessment of MMD patients.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679953","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":"A Phenotype-Based Score to Prioritize RNF213 p.R4810K Genotyping in Isolated Intracranial Steno-Occlusive Disease.","authors":"Dong Young Jeong, Chulhong Kim, Dougho Park, Taeyeon Kim, Sungho Ahn, Bum Joon Kim, Sun U Kwon","doi":"10.1007/s12975-026-01472-3","DOIUrl":"10.1007/s12975-026-01472-3","url":null,"abstract":"<p><strong>Background: </strong>Ring finger protein 213 (RNF213) p.R4810K is a genetic susceptibility factor for intracranial arteriopathies. In patients with isolated intracranial arterial steno-occlusive disease (ICAD) without Moyamoya disease (MMD), we developed a phenotype-based triage score to prioritize RNF213 genotyping by enriching the p.R4810K carriage probability.</p><p><strong>Methods: </strong>We retrospectively analyzed 753 patients with isolated ICAD involving the distal internal carotid artery or middle cerebral artery M1 segment who underwent RNF213 genotyping between January 2010 and November 2022, excluding definite MMD or significant extracranial steno-occlusion. A prespecified score incorporated anterior cerebral artery (ACA) laterality (0/1/2), tandem lesion burden ≥ 3 (0/1), and MMD family history (0/1; weighted ×4). Discrimination, prespecified thresholds (≥ 3 and ≥ 4), and bootstrap-corrected calibration were assessed, with external application in an independent cohort.</p><p><strong>Results: </strong>RNF213 p.R4810K was identified in 289 patients (38.4%). MMD family history showed the strongest association with carriage (adjusted odds ratio [OR] 8.34, 95% confidence interval [CI]: 4.15-16.77, p < 0.001), followed by tandem burden ≥ 3 (adjusted OR 1.76, 95% CI: 1.15-2.69, p = 0.009) and ACA laterality (adjusted OR 1.74, 95% CI: 1.35-2.23, p < 0.001). The score showed moderate discrimination (internal area under the curve [AUC] 0.720; external AUC 0.708). A cutoff ≥ 3 restricted genotyping to 33.5% of patients while capturing 55.7% of carriers, reducing genotyping workload by 66.5%. A cutoff ≥ 4 increased the positive predictive value to 81.7% with 97.6% specificity.</p><p><strong>Conclusions: </strong>In clinically selected isolated ICAD, a phenotype-based score incorporating lesion distribution and family history may help prioritize RNF213 genotyping and improve genotyping yield in resource-limited settings.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654483","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":"Effects of Antioxidant DI-3-N-Butylphthalide on Hemorrhagic Transformation Assessed by Propensity Score Matching in a Real-World Thrombolyzed Ischemic Stroke Patient Setting.","authors":"Ziqi Han, He Liang, Tieping Fan, Mario Minor Murakami Junior, Shumin Li, Ruikang Sun, Daoyong Peng, Shiwei Du, Yu Hasegawa, Haojie Gao, Dong Chen, Dirk M Hermann, Yi Liu","doi":"10.1007/s12975-026-01470-5","DOIUrl":"10.1007/s12975-026-01470-5","url":null,"abstract":"<p><strong>Background: </strong>Hemorrhagic transformation (HT) remains a major complication limiting the clinical utility of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients. Dl-3-N-butylphthalide (dl-NBP), a neuroprotective agent, which has beneficial effects on post-ischemic microcirculation, oxidative stress, and blood-brain barrier integrity, may potentially mitigate this risk.</p><p><strong>Methods: </strong>Using propensity score matching (1:1), this study analyzed 1,541 AIS patients of the prospective Dalian Single-center Study on Intravenous Thrombolysis for Ischaemic Stroke (DATIS) cohort treated at Central Hospital of Dalian University of Technology. Patients were stratified into combination therapy (alteplase + dl-NBP, n = 674) and monotherapy (alteplase alone, n = 674) groups. Dl-NBP (25 mg in 100 ml, 0.9% saline) was administered within 12 h after admission and followed by twice-daily doses of the same fomulation during hospitalization in the combination therapy group. Primary outcomes included the incidence of HT assessed post-thrombolysis and symptomatic intracranial hemorrhage (sICH) defined as radiographic hemorrhage occurring within 7 days post-thrombolysis and accompanied by clinical deterioration or an increase in NIHSS score ≥ 4 points. Neurological deficits at admission and at discharge were assessed using the National Institutes of Health Stroke Scale (NIHSS).</p><p><strong>Results: </strong>After propensity score matching (674 patients combination therapy vs. 674 patients monotherapy), baseline characteristics were balanced (p > 0.05 for all influence variables). The alteplase + dl-NBP combination therapy group demonstrated significantly lower HT rates (2.2% vs. 6.7%, p < 0.001) and sICH incidence (0.9% vs. 3.4%, p < 0.001) than the alteplase monotherapy group. Multivariate analysis identified dl-NBP adjuvant as protective against HT (OR = 0.32, 95%CI: 0.18-0.58), while fasting glucose (OR = 1.10) and high-density lipoprotein levels (OR = 2.25) were independent risk factors. The percentage of patients exhibiting NIHSS improvements during hospitalization was significantly increased in combination therapy group compared with monotherapy group (60.8 vs. 55.3%, p = 0.041). Hospitalization costs were slightly higher in the combination therapy group (¥20,781 vs. ¥19,771, p < 0.001).</p><p><strong>Conclusions: </strong>Early adjunctive dl-NBP administration in addition to alteplase-induced thrombolysis significantly reduces hemorrhagic complications. To our knowledge, this is the first large-scale real-world study to demonstrate that dl-NBP reduces the risk of post-thrombolytic brain hemorrhage, supporting its antioxidant benefits in a clinical setting.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631662","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":"A Ubiquitous Blood Flow Biomarker to Calculate Hypoxic-Ischemic Depolarization Latency in a Mouse Model of Focal Ischemic Stroke: Insight Into Metabolic and Electrophysiological Resilience.","authors":"Arthur Noya, Andreia Morais, Mei Li, Jeong Hyun Lee, Fumiaki Oka, Xuyan Jin, Takahiko Imai, Sanem Aykan, Aylin Uner Bozdayi, Refik Bozdayi, Tao Qin, Cenk Ayata","doi":"10.1007/s12975-026-01485-y","DOIUrl":"10.1007/s12975-026-01485-y","url":null,"abstract":"<p><p>Focal cerebral ischemia, when sufficiently severe and prolonged, culminates in a near-complete loss of neuronal membrane potential in the ischemic core, known as hypoxic-ischemic depolarization (HID). The vasoconstrictive effect of HID causes an abrupt reduction in tissue blood flow. This cerebral blood flow signature marks the onset of HID and is easily detectable by conventional laser Doppler flowmetry or full-field optical imaging techniques. Using this blood flow signature in a model of endovascular filament occlusion of the middle cerebral artery (MCAO), we conducted a large retrospective study to investigate the latency between the onset of ischemia and HID. Leveraging aggregate laser Doppler flowmetry recordings (n = 289 mice) from several independent projects in our laboratory over a decade (2016-2025), we examined the robustness of HID latency as a biomarker, its biological and procedural predictors, and its ability to predict subsequent tissue outcome. We found that younger age (p = 0.008) and lower residual cerebral blood flow (p < 0.001) accelerate HID onset, while hypothermia (p = 0.029) and NMDA receptor blockade (p = 0.012) delay it. Furthermore, regression analysis shows that faster HID onset is associated with larger cortical, subcortical, and total infarct volumes (p = 0.005, 0.012, and 0.011, respectively) after MCAO. Altogether, our data suggest that HID latency, estimated from its hemodynamic signature in routine blood flow recordings during MCAO, can be a useful biomarker of metabolic and electrophysiological resilience in focal cerebral ischemia.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631630","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 Between Inflammatory Biomarkers And Carotid Ultrasound Parameters In The Northern Manhattan Stroke Study.","authors":"Farid Khasiyev, Minghua Liu, Mady Hornig, Mohammed Nafeli Shahrestani, Clinton B Wright, Mitchell Sv Elkind, Tatjana Rundek, Jose Gutierrez","doi":"10.1007/s12975-026-01477-y","DOIUrl":"10.1007/s12975-026-01477-y","url":null,"abstract":"<p><p>Inflammation contributes to atherosclerosis and vascular remodeling, but the immune pathways associated with distinct carotid ultrasound phenotypes, including carotid intima-media thickness (cIMT), maximal plaque thickness (MPT), and arterial stiffness remain incompletely characterized. We investigated associations between circulating immune biomarkers and carotid ultrasound measures in a stroke-free, multi-ethnic cohort. We analyzed data from 1,134 stroke-free participants (mean age 70 ± 9 years, 59% women, 66% Hispanic) in the Northern Manhattan Study (NOMAS) who underwent high-resolution B-mode carotid ultrasound. cIMT and MPT were measured using automated edge-detection software, while arterial stiffness was assessed via systolic and diastolic diameter measurements, strain, and β-stiffness. Plasma levels of 60 immune biomarkers were quantified using a multiplex immunoassay. Biomarker selection was performed using LASSO, Random Forest, and XGBoost; markers selected by ≥ 2 methods were prioritized. Associations were tested using multivariable linear regression adjusted for age, sex, race/ethnicity, and cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, and smoking). Machine-learning analyses identified partially distinct candidate biomarker profiles for cIMT, MPT, and arterial stiffness. In fully adjusted regression models, greater cIMT was associated with higher IL-4 and leptin levels and lower IL-10, VCAM-1, and SerpinE1 levels. None of the machine-learning-selected biomarkers was independently associated with MPT at the conventional p < 0.05 threshold. Greater arterial stiffness was associated with higher SCF levels, while CXCL10 demonstrated a nonsignificant inverse trend. Models incorporating the selected biomarkers had modestly higher adjusted R² values than models containing clinical covariates alone (cIMT, 0.072 versus 0.109; MPT, 0.134 versus 0.147; arterial stiffness, 0.063 versus 0.075). In a stroke-free, multiethnic cohort, machine-learning analyses identified distinct and overlapping candidate immune biomarker profiles across cIMT, plaque thickness, and arterial stiffness. However, only a subset of selected biomarkers demonstrated independent associations in fully adjusted regression models. These findings support a hypothesis-generating role for inflammatory and immunometabolic pathways in subclinical carotid disease and vascular aging and require validation in longitudinal studies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593284","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":"Efficacy and Mechanisms of Combined Central-Peripheral Magnetic Stimulation on Prefrontal-Sensorimotor Cortex Connectivity in Post-Stroke Dysphagia after Supratentorial Stroke: A Randomized, Single-Blind, Parallel-Controlled Trial.","authors":"Zirui Luo, Zhiying Zhu, Yujue Wang, Na Su, Yajing Xue, Wanqi Zhang, Wei Liao, Yaoyao You, Lin Ling, Mei Li, Junjie Liang, Zulin Dou, Haian Mao, Nenggui Xu","doi":"10.1007/s12975-026-01482-1","DOIUrl":"10.1007/s12975-026-01482-1","url":null,"abstract":"<p><strong>Background: </strong>Combined central-peripheral magnetic stimulation shows promise for post-stroke dysphagia (PSD), but its neural mechanisms remain unclear. We evaluated the its efficacy and cortical mechanisms in PSD patients.</p><p><strong>Methods: </strong>In this single-blind, parallel-controlled trial, 44 PSD patients were randomized to four groups: active-rTMS + active-rPMS, active-rTMS + sham-rPMS, sham-rTMS + active-rPMS, or sham-rTMS + sham-rPMS. Clinical scales, such as functional oral intake scale (FOIS) and Penetration-Aspiration Scale (PAS), and Videofluoroscopic Swallowing Study (VFSS) were accessed before, after intervention. Cortical activation during rest and swallowing task was measured by functional near-infrared spectroscopy (fNIRS).</p><p><strong>Results: </strong>Significant interaction effects (time × intervention) were found for FOIS (Wald χ² = 39.816, p < 0.001) and PAS scores (Wald χ² = 45.433, p < 0.001), with the active-rTMS + active-rPMS group showing the most pronounced therapeutic gains. Concurrently, this group displayed significant improvements of laryngeal vestibular closure duration (LCD, MD = -3.598, 95% CI -4.177 to -3.019, adjusted p < 0.001) and superior hyoid excursion (SHE, MD = -3.708, 95% CI -4.213 to -3.18, adjusted p < 0.001). Neurophysiologically, increased functional connectivity (FC) within the ipsilesional prefrontal-sensorimotor network was observed and the changes of FC in ipsilesional M1 and S1 is significantly correlated with the change magnitude of LCD (r_s = 0.78, p = 0.004) and SHE (r_s = 0.67, P = 0.023).</p><p><strong>Conclusions: </strong>The combined central-peripheral magnetic stimulation robustly improved swallowing function, temporal and kinematic sequence of swallowing, and sensori-motor connectivity in PSD patients, representing a promising neuromodulatory therapy for PSD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580161","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":"Lipoprotein(a) -Related Cognitive Vulnerability After Stroke Beyond High-Sensitivity C-Reactive Protein.","authors":"Dandan Wang, Yue Zheng, Yuesong Pan, Mengxing Wang, Tingfang Ai, Xingquan Zhao, Yongjun Wang, Jingjing Li","doi":"10.1007/s12975-026-01483-0","DOIUrl":"10.1007/s12975-026-01483-0","url":null,"abstract":"<p><p>Post-stroke cognitive impairment (PSCI) reflects vulnerability to cognitive decline beyond acute brain injury. Lipoprotein(a) (Lp(a)) is a genetically determined vascular risk factor with pro-inflammatory and pro-atherogenic properties, but the pathways linking Lp(a) to cognitive outcomes after stroke remain unclear. We examined whether systemic inflammation mediates or modifies Lp(a)-related cognitive risk after ischemic stroke. We analyzed data from a prespecified substudy of the Third China National Stroke Registry. Baseline serum Lp(a) and high-sensitivity C-reactive protein (hs-CRP) were measured. PSCI was defined as a Montreal Cognitive Assessment score ≤ 22 at 1 year. Multivariable logistic regression, interaction, joint exposure, and causal mediation analyses were performed to evaluate the role of systemic inflammation in the Lp(a)-PSCI association. Among 954 patients with acute ischemic stroke, higher baseline Lp(a) was associated with increased PSCI risk after adjustment for baseline cognitive performance and clinical covariates (highest vs. lowest tertile: OR, 1.479; 95% CI, 1.007-2.170). In contrast, hs-CRP was not independently associated with PSCI after multivariable adjustment. No significant multiplicative interaction between Lp(a) and hs-CRP was observed (P = 0.2026). Although joint exposure analyses showed the highest PSCI risk among patients with both elevated Lp(a) and hs-CRP, mediation analysis did not support hs-CRP as a meaningful mediator (proportion mediated = 1.46%). These findings suggest that the observed association between Lp(a) and PSCI was not substantially explained by hs-CRP-indexed peripheral systemic inflammation. Elevated Lp(a) was associated with PSCI independently of baseline cognitive performance, but this association was not mediated or significantly modified by hs-CRP. Lp(a)-related cognitive vulnerability after ischemic stroke may therefore reflect vascular susceptibility not captured by hs-CRP alone, with hs-CRP-defined systemic inflammation contributing to cumulative risk rather than serving as the primary mechanistic pathway.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563026","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":"Ischemic Stroke Increases Protein Expression of the Folate Receptor and One-carbon Enzymes in Brain Tissue From Male and Female Patients.","authors":"Petter Burrows, Himmat Dhillon, Gillian E McDemott, Amanda Covaleski, Lilah Manfredi, Thomas G Beach, Geidy E Serrano, Nafisa M Jadavji","doi":"10.1007/s12975-026-01479-w","DOIUrl":"10.1007/s12975-026-01479-w","url":null,"abstract":"<p><p>Stroke is the second most common cause of death worldwide and predominantly affects individuals over 65 years old. Its prevalence is projected to increase in parallel with the aging global population. Nutrition is a modifiable risk factor for ischemic stroke. Folates, B-vitamins and choline play a central role in one-carbon metabolism (1 C), which is a key metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, epigenetics, regulation of cell proliferation, and stress resistance. Using preclinical models, our research group has previously shown that deficiencies in 1 C lead to worse stroke outcomes. However, the impact of ischemic stroke on 1 C enzymes in human brain tissue remains unexplored. The objective of this study is to investigate whether ischemic stroke contributes to a change in the levels of 1 C enzymes after ischemic stroke in male and female patients. Cortical brain tissue sections from ischemic stroke patients and controls were stained for enzymes involved in 1 C. All tissue was co-stained with neuronal nuclei (NeuN) and DAPI (4',6-diamidino-2-phenylindole). The colocalization of all three markers was evaluated by two individuals who were masked to the experimental groups. Ischemic stroke increased neuronal levels of the folate receptor and 1 C enzymes, methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and serine hydroxy methyltransferase (SHMT). In male stroke brain tissue was observed to have increased levels of MTHFR, TS, and SHMT. Female brain tissue had increases in the folate receptor and TS. The results suggest that ischemic stroke leads to changes in neuronal levels of FR and 1 C enzymes levels in penumbra. Further clinical investigation is required to determine whether there is increase enzymatic activity and how 1 C is impacted in other cells within the brain, such as glial and endothelial cells.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562992","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":"Large-Scale Plasma Proteomics Profiles for Predicting Atrial Fibrillation Associated Stroke Risk : Type of manuscript: Original Research.","authors":"Shengkang Huang, Xin Feng, Huilin Wu, Rongxuan Liang, Yuan Gao, Zhaojun Wang, Botao Tang, Jiatong Wu, Junkai Fang, Ziang Yang, Xieraili Tiemuerniyazi, Jiancheng Lin, Yijingxuan Duan, Wenru Xu, Hua Mao, Wei Zhao, Zhan Hu, Chuanzhi Duan, Wei Feng","doi":"10.1007/s12975-026-01476-z","DOIUrl":"10.1007/s12975-026-01476-z","url":null,"abstract":"<p><strong>Background: </strong>Stroke is a major complication of atrial fibrillation (AF), and risk prediction using the congestive heart failure, hypertension, age, diabetes, stroke, vascular disease, and sex category score (CHA₂DS₂-VASc) remains limited by residual heterogeneity. We aimed to identify plasma proteins associated with post-AF stroke and evaluate whether a protein score provides incremental predictive information beyond CHA₂DS₂-VASc.</p><p><strong>Methods: </strong>We analyzed 709 AF participants from the UK Biobank Pharma Proteomics Project, with 76 incident strokes. Stroke-related proteins were identified using multivariable Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and machine-learning approaches. A five-protein score was constructed, and its incremental value beyond CHA₂DS₂-VASc was assessed by discrimination, calibration, reclassification, clinical net benefit, and 1000-bootstrap internal validation. Mendelian randomization served as supportive genetic evidence.</p><p><strong>Results: </strong>Five core proteins were identified: epidermal growth factor receptor (EGFR), V-type proton ATPase subunit D (ATP6V1D), neurotrophin 4 (NTF4), amnionless (AMN), and discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2). Adding the five-protein score to CHA₂DS₂-VASc improved discrimination, increasing the concordance index from 0.681 to 0.768. The combined model had 3-, 5-, and 8-year receiver operating characteristic areas of 0.799, 0.775, and 0.806, respectively, and showed favorable five-year prediction error and calibration, with a Brier score of 0.0347, calibration intercept of -0.068, and calibration slope of 0.968. The score improved continuous net reclassification improvement (0.459; P = 0.028). Mendelian randomization provided supportive genetic evidence for AMN, EGFR, and DCBLD2.</p><p><strong>Conclusions: </strong>The five-protein score provided incremental predictive information beyond CHA₂DS₂-VASc for post-AF stroke risk assessment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563011","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":"Loss of Vascular TMEM16A Impairs Cerebral Autoregulation and Exacerbates Ischemia-reperfusion Injury.","authors":"Ask Carit Andersen, Ida Damsgaard Larsen, Elizaveta V Melnikova, Marlon Gernemann, Boris V Skryabin, Tina Myhre Pedersen, Hans Christian Beck, Halvor Østerby Guldbrandsen, Eugenio Gutierrez, Christian Aalkjaer, Dmitry D Postnov, Vladimir V Matchkov, Line Mathilde Brostrup Hansen","doi":"10.1007/s12975-026-01471-4","DOIUrl":"10.1007/s12975-026-01471-4","url":null,"abstract":"<p><p>TMEM16A forms a Ca²⁺-activated Cl⁻ channel in vascular mural cells (smooth muscle cells and pericytes) that generates depolarizing Cl⁻ efflux upon intracellular Ca²⁺ elevation, thereby amplifying agonist-induced vasoconstriction. TMEM16A has been implicated in excessive capillary pericyte constriction following cerebral ischemia, suggesting that its inhibition may improve post-stroke recovery. However, the impact of systemic vascular TMEM16A inhibition on focal reperfusion efficiency and cerebrovascular autoregulation remains unknown. To address this question, mice with inducible mural cell-specific (Myosin Heavy Chain 11 promoter controlled) deletion of TMEM16A were subjected to transient middle cerebral artery occlusion. Reperfusion dynamics and stroke-reperfusion outcome were assessed using laser speckle contrast imaging, cylinder test for motor function, and infarct quantification by 2,3,5-triphenyltetrazolium chloride staining. Systemic cardiovascular parameters were monitored with radiotelemetry. Middle cerebral artery myogenic tone was assessed with pressure myography. Mice lacking TMEM16A in mural cells exhibited impaired reperfusion and worsened stroke outcome compared with wild-type controls, despite unchanged systemic cardiovascular parameters. In wild-type mice, capillary pericytes maintained basal contractile tone in both hemispheres, and this was further enhanced in peri-infarct cortex. In contrast, TMEM16A-deficient capillary pericytes lacked basal tone in both the ipsilateral and contralateral hemispheres. TMEM16A-deficient middle cerebral arteries failed to develop pressure-induced myogenic tone. These findings demonstrate that TMEM16A is required for effective cerebral autoregulation and that its deficiency significantly impairs post-ischemic reperfusion. The results caution against systemic TMEM16A inhibition as a therapeutic strategy for stroke and highlight the need for spatially restricted approaches to modulate cerebral perfusion via the Ca²⁺-activated Cl⁻ channels.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550668","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}