Translational Stroke Research最新文献

{"title":"Plasma Metabolic Signature and Single-Cell Regulatory Network for Ischemic Stroke.","authors":"Zhiyuan Guo, Haijun Zhang, Liwei Lv, Ping Ding, Lingyan Qi, Xiaokun Wang, Yan Chen, Yingshui Yao, Liyuan Han","doi":"10.1007/s12975-026-01429-6","DOIUrl":"10.1007/s12975-026-01429-6","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a leading cause of mortality and long-term disability worldwide, with ultra-early diagnosis critical for effective reperfusion therapy but challenged by nonspecific symptoms and limited sensitivity of imaging in the hyperacute phase. Plasma metabolomic alterations occur rapidly after ischemia onset, offering potential for accessible biomarkers and deeper insights into underlying pathogenic mechanisms. We therefore aimed to explore plasma metabolic alterations and their associated regulatory networks in IS. We conducted a multicenter case–control study involving 493 IS patients and 493 controls individually matched for age, sex, and body mass index (BMI). Untargeted LC–MS-based metabolomic profiling was performed on plasma samples to quantify and identify differentially abundant metabolites. Machine learning models, including LASSO and XGBoost, were used to select diagnostic biomarkers and construct a classification model. Model performance was evaluated using ten-fold cross-validation, an internal test set, and two independent external validation cohorts. Core regulatory genes were identified by integrating metabolite-related genes from HMDB with transcriptomic data from the GEO dataset. Functional enrichment, single-cell RNA sequencing, and drug-gene interaction analyses were further employed. We identified 319 endogenous differential metabolites, among which 18 core metabolites were selected to build an XGBoost diagnostic model. L-Methionine (Log2FC = 4.97), Purine (Log2FC = − 3.12), and Threonic acid (Log2FC = − 1.74) were the most influential contributors. The metabolite-based model showed strong internal discrimination under ten-fold cross-validation and internal testing; however, external validation was heterogeneous, with substantially reduced discrimination in the Ningbo cohort and preserved performance in the Suzhou cohort. This pattern suggests center-dependent variability and potential optimism in internally estimated performance, warranting cautious interpretation. Furthermore, ten core regulatory genes (e.g., MAOA, MSRB2, ACSM2A) were identified and implicated in neurotransmitter metabolism, oxidative stress, and fatty acid activation. Single-cell analysis revealed cell-type-specific expression patterns of the detectable core genes in endothelial cells and microglia. Drug prediction highlighted several repurposable compounds, including levodopa and tryptamine, with predicted binding affinity to target proteins. This multi-omics study characterizes a plasma metabolic signature associated with IS while highlighting cohort-dependent variability in external validation. Although internally derived diagnostic performance was high, heterogeneous external validation underscores the importance of cautious interpretation and prospective real-world validation. Overall, these findings should be regarded as hypothesis-generating and require confirmation in larger, consecutively recruited real-world populations.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515037","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":"Decompressive Craniectomy Decreases Neuroinflammation after Ischemic Stroke in Mice.","authors":"Josephine Malczuk, Jonathane Furon, Emmie Coué, Maxime Gauberti, Lucile Sandberg, Anthony Levilly, Alin Borha, Evelyne Emery, Denis Vivien, Thomas Gaberel","doi":"10.1007/s12975-026-01423-y","DOIUrl":"10.1007/s12975-026-01423-y","url":null,"abstract":"<p><p>In human, decompressive craniectomy (DC) reduces morbi-mortality of malignant stroke. Because the cranial vault carries hematopoietic niches hosting inflammatory cells, we used here a preclinical model of stroke and DC in mice to evaluate whether the removal of the cranial vault may influence neuroinflammation after malignant stroke. 99 C57/BL6 mice were used, and stroke was induced using a filament model. Mice were randomized in 4 groups: Sham (n = 15), Stroke (n = 40), DC (n = 18) and Stroke + DC (n = 26). The inflammatory response was evaluated at D1 and D5 by using both non-invasive molecular MRI of VCAM-1 signal void and flow cytometry analyses of a large set of immune cells. Molecular MRI of VCAM-1 revealed a massive endothelial inflammatory status after stroke, a process reduced by DC at day 1 and day 5. We also revealed that DC reduced levels of border-associated macrophages (BAMs) induced by stroke in the ipsilateral hemisphere, which was associated with an increase of BAMs in the contralateral hemisphere. Effect on inflammatory processes in the contralateral hemisphere was also confirmed by a decrease of parenchymal T-cells (CD3+) in the DC group as compared to the Stroke group. DC reduces post-stroke cerebral inflammation, as shown by molecular MRI, and may modulate BAM and parenchymal T-cell distribution.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469365","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":"Accounting for Truncation Artifacts in Angiographic Perfusion.","authors":"Kyle A Lyman, Ryan M Hebert, Charles C Matouk, Kevin N Sheth, Guido J Falcone, W Taylor Kimberly, David Y Chung, Nils H Petersen, Ona Wu","doi":"10.1007/s12975-026-01420-1","DOIUrl":"10.1007/s12975-026-01420-1","url":null,"abstract":"<p><p>Unlocking perfusion metrics from routine digital subtraction angiography could transform how neurovascular disease is managed. Truncation artifact, defined as premature termination of image acquisition, is a key source of error in CT and MR perfusion imaging. However, length requirements for deriving perfusion metrics from angiography remain undefined. This study investigates the minimum image acquisition length required for interpreting mean transit time from digital subtraction angiography. We analyzed 55 outpatient angiograms performed for surveillance an average of 687 days after aneurysmal rupture. Truncation artifact was simulated by progressively shortening the angiography runs after bolus arrival. A gamma-variate function was used to assess if extrapolation of the truncated data could approximate full length acquisitions. Extrapolation of the truncated datasets with the gamma-variate function produced highly reliable estimates of the mean transit time with at least seven seconds of post-bolus data (mean difference between truncated/extrapolated MTT and original MTT 0.003 ± 0.047 s, mean ± SD). The fraction of pixels fit by the gamma-variate function was also sensitive to truncation and at least seven seconds of data was required to fit > 90% of the pixels. These findings provide a framework for evaluating the adequacy of image acquisition time and lay the foundation for retrospective perfusion analysis using digital subtraction angiography.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443895","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":"Remote Ischemic Preconditioning Exerts Neuroprotective Effects Via the PGC-1α/FNDC5/BDNF Pathway in Focal Brain Ischemia of Rats.","authors":"Teruki Matsuoka, Ryoma Matsuzaki, Kazuki Nakanishi, Shogo Kakimoto, Yuki Kato, Shotaro Otsuka, Kiyoshi Kikuchi, Harutoshi Sakakima","doi":"10.1007/s12975-026-01422-z","DOIUrl":"10.1007/s12975-026-01422-z","url":null,"abstract":"<p><p>Remote ischemic preconditioning (RIpreC) is a strategy for remotely protecting target organs such as the brain by applying brief ischemia and reperfusion to the limb. However, the mechanisms underlying RIpreC-induced neuroprotection remain unclear. We aimed to investigate the neuroprotective effects of RIpreC on the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)/ fibronectin type III domain-containing protein 5 (FNDC5)/ brain-derived neurotrophic factor (BDNF) pathway in rat models of ischemic stroke. Rats were assigned to three groups: ischemia-reperfusion injury (IR, n = 11), RIpreC and IR (RIpreC, n = 11), and intact control (control, n = 5). RIpreC was performed approximately 24 h before IR injury. IR injury induced by middle cerebral artery occlusion (MCAO) for 60 min. At 2 days after MCAO, brain infarction, sensorimotor functions, and the expression of PGC-1α, FNDC5/irisin, BDNF, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL)-positive cells, and the p-Akt/Akt ratio were examined. In addition, SR-18,292, a PGC-1α inhibitor, was administered 1 h before MCAO. The RIpreC group had a significantly reduced infarct volume and ameliorated sensorimotor function compared with the IR group. RIpreC increased the expression of PGC-1α, FNDC5, BDNF, and the p-Akt/Akt ratio in the ischemic brain. Bax/Bcl-2 ratios, as well as perilesional caspase-3- and TUNEL-positive neuronal cells, decreased following RIpreC. Inhibition of PGC-1α blunted the RIpreC-induced neuroprotective and neurorestorative effects. This study suggests that RIpreC induced BDNF expression through a PGC-1α/FNDC5 pathway after ischemic stroke, thereby exerting neuroprotection and ameliorating post-stroke neurobehavioral dysfunctions.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378641","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":"Comprehensive Evaluation of Predictive Significance of FABP4 for Long-term Clinical Outcomes After Ischemic Stroke.","authors":"Youdan Tu, Pei Feng, Lulu Sun, Yanyu Zhu, Suyang Wu, Yanbo Peng, Yonghong Zhang, Tan Xu, Chongke Zhong, Guodong Xiao","doi":"10.1007/s12975-026-01425-w","DOIUrl":"10.1007/s12975-026-01425-w","url":null,"abstract":"<p><p>Fatty acid-binding protein 4 (FABP4) has been reported to be involved in cerebral ischemia injury by modulating neurological function and inflammatory responses. This study aimed to investigate the association between plasma FABP4 levels and long-term, comprehensive clinical outcomes after acute ischemic stroke. Plasma FABP4 levels were measured in 3352 patients with acute ischemic stroke from the Chinese Acute Ischemic Stroke Antihypertensive Trial. Primary outcome was the composite of death and major disability (modified Rankin Scale score ≥ 3); secondary outcomes included major disability, all-cause mortality, stroke-specific mortality, and cardiovascular events. After 24-month follow-up, 790 patients experienced primary outcome, including 502 major disability and 288 all-cause mortality. Compared with the lowest tertile, the highest tertile of FABP4 was associated with primary outcome (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.27-2.00), major disability (OR 1.40, 95% CI 1.09-1.82), all-cause mortality (hazard ratio [HR] 1.58, 95% CI 1.15-2.17), stroke-specific mortality (HR 1.68, 95% CI 1.17-2.40), and cardiovascular events (HR 1.35, 95% CI 1.02-1.80). Adding FABP4 to the basic model with conventional risk factors significantly improved risk reclassification for primary outcome (net reclassification improvement: 24.95%; integrated discrimination index: 0.75%). FABP4 was among the top five important predictors for primary outcome, ranking higher than N-terminal pro-brain natriuretic peptide and other biomarkers. Elevated plasma FABP4 levels were associated with increased risks of a variety of adverse outcomes after ischemic stroke at 24 months, suggesting that FABP4 could serve as a promising biomarker to improve risk stratification for long-term prognosis in ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366607","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 Influence of M1 and DLPFC iTBS on BCI Performance: A TMS and fNIRS Study.","authors":"Jing Chen, Ya-Wen Li, Shan-Tong Yao, Yu-Hong Huang, Wen-Ming Ma, Zhi-Hong Li, Yue Lan, Guang-Qing Xu, Qian Ding","doi":"10.1007/s12975-026-01424-x","DOIUrl":"10.1007/s12975-026-01424-x","url":null,"abstract":"<p><p>Brain-computer interface (BCI) control inefficiency often occurs in stroke survivors due to insufficient sensorimotor activity generated during motor imagery. Previous studies focused on upregulating excitability of primary motor cortex (M1) alone. Dorsolateral prefrontal cortex (DLPFC), an important region for motor imagery, may be effective for improving BCI performance. This study is aimed at investigating how intermittent theta burst stimulation (iTBS) targeted on M1 and DLPFC influences BCI performance and its neural mechanisms.25 healthy subjects (9 males) received four types of iTBS (i.e., M1 iTBS, DLPFC iTBS, combination of M1 and DLPFC iTBS and sham iTBS) on separate days. BCI control testing, functional near-infrared spectroscopy assessment and single-pulse transcranial magnetic stimulation were performed before and immediately after iTBS in each session. Corticospinal excitability, brain activation, and functional connectivity were calculated. Our results revealed that corticospinal excitability was significantly increased after M1 iTBS (P = 0.016), with the magnitude of increase positively correlated with BCI performance (P = 0.013). Frontoparietal network functional connectivity was significantly increased after DLPFC iTBS (P's<0.05), with the magnitude of increase positively correlated with changes in BCI performance (P's<0.05). In conclusion, M1 iTBS and DLPFC iTBS alone influences BCI performance through specific neural mechanisms, and the combination of M1 and DLPFC iTBS did not induce any significant results. M1 iTBS could influence BCI performance by enhancing corticospinal excitability, while DLPFC iTBS could influence BCI performance by increasing frontoparietal network connectivity. These findings could contribute to the advancement of novel therapeutic strategies aimed at enhancing BCI effectiveness for neurological populations. Trial registration: The study was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2500097678). Registration Date: 2025-02-24.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327236","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":"Cerebrolysin after Endovascular Thrombectomy in Stroke: 12‑Month Functional Outcomes in a Propensity‑Matched Cohort.","authors":"Jacek Staszewski, Aleksander Dębiec, Katarzyna Gniadek-Olejniczak, Adam Stępień, Renata Piusinska-Macoch, Stefan Strilciuc, David Balo, George Harston, Krzysztof Brzozowski, Piotr Zięcina, Jerzy Narloch, Marek Wierzbicki, Piotr Piasecki","doi":"10.1007/s12975-026-01414-z","DOIUrl":"10.1007/s12975-026-01414-z","url":null,"abstract":"<p><p>Background Long-term outcomes after endovascular thrombectomy (EVT) and the role of adjunctive neuroprotection to achieve post-stroke independence remain incompletely characterized. In this hypothesis-generating target-trial emulation, we assessed 12-month functional outcomes in a prespecified extension of a propensity score-matched cohort of rigorously selected EVT patients treated with adjunctive Cerebrolysin, a multimodal neuroprotective agent. Methods Consecutive EVT patients were prospectively enrolled and treated with Cerebrolysin 30 mL/day for 21 days starting immediately post-EVT, with a second 21-day course at 69-90 days. Outcomes were compared with historical controls using 1:1 nearest-neighbor propensity score matching on ten prespecified covariates. The primary endpoint was functional independence (modified Rankin Scale [mRS] 0-2) at 12 months. Secondary endpoints included 12-month mRS shift, Barthel Index (BI), and need for institutional care. Multivariable regression models were used to estimate adjusted associations, with prespecified sensitivity analyses including calendar time and key EVT predictors. Results Cerebrolysin use was associated with higher odds of 12-month functional independence after adjustment for potential confounders (aOR 6.10, 95% CI 1.64-22.66; p<0.01) and a favorable shift toward lower disability across the 12-month mRS distribution (common OR for favorable shift 3.57, 95% CI 1.42-8.93; p<0.01). Cumulative 12-month mortality was similar between groups (both 18%). Among survivors, 6% of the Cerebrolysin group versus 19% of controls required institutional care (unadjusted OR 0.26; 95% CI 0.07-0.99; NNT 8). BI scores were higher in the Cerebrolysin group than in controls (median (Q1-Q3) 92 (82-100) vs 83 (73-93); p=0.01). In multivariable models, Cerebrolysin remained associated with 12-month independence alongside complete reperfusion (mTICI 3), lower post-EVT NIHSS, fewer device passes, and absence of symptomatic intracranial hemorrhage. Conclusions In EVT-treated patients selected for a small infarct core, robust collaterals, and high-quality reperfusion, adjunctive Cerebrolysin showed a potential benefit toward better 12-month functional outcomes. These exploratory findings require confirmation in multicenter randomized trials to establish efficacy and refine patient selection.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285254","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":"Blood Clot Classification in Ischemic Stroke Patients using ESAFH-Net with Explainable AI.","authors":"G Kanagaraj, S Rajeshkumar, Vivekrabinson K, Bharath Singh J","doi":"10.1007/s12975-026-01411-2","DOIUrl":"10.1007/s12975-026-01411-2","url":null,"abstract":"<p><p>Accurate classification of blood clots in ischemic stroke patients is vital for effective treatment planning. Nonetheless, difficulties like subtle visual differences and complicated clot structures make manual diagnosis time-consuming and error-prone. This article introduces an innovative model named the Efficient Shuffle Attention Forward Harmonic Network (ESAFH-Net) for classifying blood clots in ischemic stroke patients. Unlike existing blood clot classification approaches, the proposed ESAFH-Net uniquely integrates shuffle attention with harmonic analysis within an EfficientNet backbone to capture both local and global clot characteristics. Furthermore, this study is among the first to incorporate Explainable Artificial Intelligence (XAI) for interpretable classification of Cardioembolic (CE) and Large Artery Atherosclerosis (LAA) clots using whole-slide digital pathology images. Firstly, the input whole slide digital pathology image is obtained from the given dataset. The acquired image is subjected to enhancement using Contrast Limited Adaptive Histogram Equalization (CLAHE) to enhance visual quality. Next, blood clot segmentation is performed using a Recurrent Residual Convolutional Neural Network based on U-Net (R2U-Net), with a log loss function. Thereafter, morphological features and Gray-Level Co-Occurrence Matrix (GLCM) features are mined. Finally, blood clot classification is performed using the proposed ESAFH-Net, enabling differentiation between CE and LAA types. Moreover, ESAFH-Net is a hybrid model that incorporates EfficientNet, Shuffle Attention Network (SA-NET), and harmonic analysis. Furthermore, the interpretability of the proposed technique is validated using XAI. The efficacy of ESAFH-Net is validated employing evaluation measures, achieving a True Positive Rate (TPR) of 92.885%, an accuracy of 92.595%, and a False Positive Rate (FPR) of 7.617%.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277039","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":"Correction to: Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury after SAH.","authors":"Yang Liu, Chenbei Yao, Bin Sheng, Simin Zhi, Xiangxin Chen, Pengfei Ding, Jiatong Zhang, Zhennan Tao, Wei Li, Zong Zhuang, Jiannan Mao, Zheng Peng, Huiying Yan, Wei Jin","doi":"10.1007/s12975-026-01418-9","DOIUrl":"10.1007/s12975-026-01418-9","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 2","pages":"26"},"PeriodicalIF":4.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207824","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":"Single-Cell Multiomics Decoding of TCIRG1-Mediated Cuproptosis Circuitry Rewiring Immune-Metabolic Landscape in Ischemic Stroke.","authors":"Jiajun Zhou, Ling Chen, Junheng Li, Lian Luo, Sen Shao","doi":"10.1007/s12975-025-01406-5","DOIUrl":"10.1007/s12975-025-01406-5","url":null,"abstract":"<p><p>Ischemic stroke is one of the leading causes of disability and mortality worldwide. Its pathogenesis extends beyond focal cerebral ischemia-induced neuronal injury, encompassing profound immune dysregulation and secondary inflammatory responses. Recent studies have highlighted T cell dysfunction, particularly T cell exhaustion, as a critical driver of post-stroke immunosuppression and increased susceptibility to infection. However, the molecular mechanisms underlying this process remain unclear. This study focuses on a novel immunoregulatory axis involving cuproptosis, metabolic reprogramming, and T cell exhaustion, and systematically investigates the role of the key regulatory molecule TCIRG1 in post-ischemic immune homeostasis disruption. Through integrative analysis of human peripheral blood transcriptomic data (GSE58294) and single-cell transcriptomic datasets from mouse brain and bone marrow following middle cerebral artery occlusion (MCAO) (GSE174574 and GSE293098), we found that the cuproptosis pathway was markedly activated after ischemic stroke. Notably, TCIRG1 was highly expressed in T cells and co-upregulated with the cuproptosis regulator Fdx1 and T cell exhaustion markers. Metabolic flux analysis revealed that high TCIRG1 expression was associated with enhanced pyruvate metabolism and was accompanied by downregulation of MYC signaling and upregulation of Zfp644, suggesting a role for TCIRG1 in driving T cell exhaustion through metabolic reprogramming. Furthermore, CellChat analysis indicated that TCIRG1 altered intercellular communication between T cells and microglia, thereby reshaping the local immune communication network. Collectively, these findings suggest that TCIRG1 may promote T cell dysfunction via cuproptosis and metabolic pathways, contributing to immune microenvironmental imbalance after ischemic stroke. This study proposes a novel multi-axis regulatory model and provides a potential molecular target for post-stroke immunotherapy.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 1","pages":"25"},"PeriodicalIF":4.2,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166789","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}