Journal of Cerebral Blood Flow and Metabolism最新文献

Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke. 利用孟德尔随机化为缺血性中风的药物发现和开发提供信息。

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2024-12-04 DOI: 10.1177/0271678X241305916

Iyas Daghlas, Dipender Gill

{"title":"Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke.","authors":"Iyas Daghlas, Dipender Gill","doi":"10.1177/0271678X241305916","DOIUrl":"10.1177/0271678X241305916","url":null,"abstract":"Discovery and development of efficacious and safe pharmacological therapies is fraught with challenges. As proteins constitute the majority of drug targets and are encoded by genes, naturally occurring genetic variation within populations can provide valuable insights to inform drug discovery and development efforts. The drug target Mendelian randomization (MR) paradigm leverages these principles to investigate the causal effects of drug targets in humans. This review examines the application of drug target MR in informing the efficacy and development of therapeutics for ischemic stroke prevention and treatment. We consider applications of MR for existing and novel treatment strategies, including targeting blood pressure, lipid metabolism, coagulation, inflammation and glycemic control. Several of these genetically supported targets are under evaluation in late-stage clinical trials. Methodological limitations of drug target MR are addressed, followed by an outline of future research directions. We anticipate that careful application of drug target MR will enhance the efficiency of drug development for ischemic stroke, consequently accelerating the delivery of effective medications to patients.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1404-1423"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769318","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}

引用次数: 0

Setting standards for brain collection procedures in metabolomic studies. 制定代谢组学研究中脑采集程序的标准。

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-01-25 DOI: 10.1177/0271678X251314331

Gerald A Dienel, Thaddeus S Nowak

引用次数: 0

Genetic determinants of insufficiency of the collateral circulation. 侧支循环不全的遗传决定因素。

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-02-04 DOI: 10.1177/0271678X251317880

James E Faber

{"title":"Genetic determinants of insufficiency of the collateral circulation.","authors":"James E Faber","doi":"10.1177/0271678X251317880","DOIUrl":"10.1177/0271678X251317880","url":null,"abstract":"It has been estimated that approximately two million neurons, sixteen billion synapses and twelve kilometers of axons are lost each minute following anterior large-vessel stroke. The level of collateral blood flow has become recognized as a primary determinant of the pace of this loss and an important factor in clinical decision-making. Many of the topics in this review cover recent developments that have not been reviewed elsewhere. These include that: the number and diameter of collaterals and collateral blood flow vary greatly in the brain and other tissues of healthy individuals; a large percentage of individuals are deficient in collaterals; the underlying mechanism arises primarily from naturally occurring polymorphisms in genes/genetic loci within the pathway that drives collateral formation during development; evidence indicates collateral abundance does not exhibit sexual dimorphism; and that collaterals-besides their function as endogenous bypass vessels-may have a physiological role in optimizing oxygen delivery. Animal and human studies in brain and other tissues, where available, are reviewed. Details of many of the studies are provided so that the strength of the findings and conclusions can be assessed without consulting the original literature. Key questions that remain unanswered and strategies to address them are also discussed.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1341-1368"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122925","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}

引用次数: 0

Elucidating stroke etiology through lipidomics of thrombi and plasma in acute ischemic stroke patients undergoing endovascular thrombectomy. 通过血管内取栓术急性缺血性卒中患者血栓和血浆脂质组学研究卒中病因。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-05-05 DOI: 10.1177/0271678X251327944

Chih-Ning Cheng, Chung-Wei Lee, Ching-Hua Lee, Sung-Chun Tang, Ching-Hua Kuo

{"title":"Elucidating stroke etiology through lipidomics of thrombi and plasma in acute ischemic stroke patients undergoing endovascular thrombectomy.","authors":"Chih-Ning Cheng, Chung-Wei Lee, Ching-Hua Lee, Sung-Chun Tang, Ching-Hua Kuo","doi":"10.1177/0271678X251327944","DOIUrl":"10.1177/0271678X251327944","url":null,"abstract":"Acute ischemic stroke (AIS) requires detailed etiology information to guide optimal management. Given the pivotal role of lipids in AIS, we conducted a comprehensive lipidomics analysis of paired thrombi and plasma from AIS patients, correlating the findings with stroke etiology. Patients were recruited across four etiologies: cardioembolism (CE), large artery atherosclerosis (LAA), active cancer (Cancer), and undetermined. Plasma and thrombi were collected before and during endovascular thrombectomy and analyzed using in-house targeted lipidomics. Among 51 patients (37 CE, 7 LAA, 4 Cancer, and 3 undetermined), we identified 37 and 70 lipid species significantly different between thrombi in CE and LAA, and CE and Cancer, respectively (FDR-corrected P < 0.05). No significant differences were observed in plasma. Notably, 21 diacylglycerols and 11 polyunsaturated triacylglycerols were depleted (2.5 to 12 folds) in LAA compared to CE, while 10 ceramides and 57 glycerophospholipids were elevated in Cancer. With 80% validation accuracy, 29 and 59 lipids distinguished LAA and Cancer from CE, respectively. A neural network model using these lipids effectively classified undetermined patients. This study emphasizes the significance of thrombus lipids in distinguishing between LAA, CE, and Cancer etiologies in AIS, enhancing our understanding of stroke pathophysiology and informing future clinical managements.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1493-1505"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009392","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}

引用次数: 0

Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling. 单细胞RNA测序在中风和创伤性脑损伤：转录组学分析的当前成就、挑战和未来展望。

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2024-12-09 DOI: 10.1177/0271678X241305914

Ruyu Shi, Huaijun Chen, Wenting Zhang, Rehana K Leak, Dequan Lou, Kong Chen, Jun Chen

{"title":"Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.","authors":"Ruyu Shi, Huaijun Chen, Wenting Zhang, Rehana K Leak, Dequan Lou, Kong Chen, Jun Chen","doi":"10.1177/0271678X241305914","DOIUrl":"10.1177/0271678X241305914","url":null,"abstract":"Single-cell RNA sequencing (scRNA-seq) is a high-throughput transcriptomic approach with the power to identify rare cells, discover new cellular subclusters, and describe novel genes. scRNA-seq can simultaneously reveal dynamic shifts in cellular phenotypes and heterogeneities in cellular subtypes. Since the publication of the first protocol on scRNA-seq in 2009, this evolving technology has continued to improve, through the use of cell-specific barcodes, adoption of droplet-based systems, and development of advanced computational methods. Despite induction of the cellular stress response during the tissue dissociation process, scRNA-seq remains a popular technology, and commercially available scRNA-seq methods have been applied to the brain. Recent advances in spatial transcriptomics now allow the researcher to capture the positional context of transcriptional activity, strengthening our knowledge of cellular organization and cell-cell interactions in spatially intact tissues. A combination of spatial transcriptomic data with proteomic, metabolomic, or chromatin accessibility data is a promising direction for future research. Herein, we provide an overview of the workflow, data analyses methods, and pros and cons of scRNA-seq technology. We also summarize the latest achievements of scRNA-seq in stroke and acute traumatic brain injury, and describe future applications of scRNA-seq and spatial transcriptomics.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1447-1471"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794855","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}

引用次数: 0

Molecular heterogeneity in human stroke - What can we learn from the peripheral blood transcriptome? 人类中风的分子异质性——我们能从外周血转录组学中学到什么？

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-03-13 DOI: 10.1177/0271678X251322598

Boryana Stamova, Bodie Knepp, Fernando Rodriguez

{"title":"Molecular heterogeneity in human stroke - What can we learn from the peripheral blood transcriptome?","authors":"Boryana Stamova, Bodie Knepp, Fernando Rodriguez","doi":"10.1177/0271678X251322598","DOIUrl":"10.1177/0271678X251322598","url":null,"abstract":"Stroke is a multifaceted disease with genetic and environmental components like diet and lifestyle. The central nervous and immune systems display complex interactions, with the peripheral immune response participating in brain injury and repair mechanisms following stroke. The bidirectional communication between the injured brain and peripheral blood presents an opportunity to investigate the molecular changes in the latter. There is substantial heterogeneity in stroke pathogenesis, pathophysiology, comorbidities, and response to treatment and outcome. This is captured and underscored by heterogeneity in the peripheral blood transcriptome. The current review highlights the role of the human peripheral blood transcriptome architecture for molecular phenotyping of different stroke etiologies and comorbidities, and for identifying underlying molecular correlates with clinically important variables and outcomes. Specific transcriptome features can potentially provide targets for clinical translation and for prioritizing genes and pathways for evaluation in experimental models. We also propose an approach to study the patient-specific transcriptional architecture and uncover the combinatorial heterogeneity in altered pathways in stroke patients that can also guide the search for treatment and prevention targets. Deciphering the molecular heterogeneity of stroke in a tissue that can be easily accessed and monitored, such as peripheral blood, may improve clinical trial success.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1424-1446"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624823","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}

引用次数: 0

Genomics of stroke recovery and outcome. 脑卒中恢复和预后的基因组学研究。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-04-11 DOI: 10.1177/0271678X251332528

Arne G Lindgren

引用次数: 0

How epigenetics impacts stroke risk and outcomes through DNA methylation: A systematic review. 表观遗传学如何通过DNA甲基化影响中风风险和结果：一项系统综述。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-02-27 DOI: 10.1177/0271678X251322032

Cristina Gallego-Fabrega, Natalia Cullell, Israel Fernández-Cadenas

{"title":"How epigenetics impacts stroke risk and outcomes through DNA methylation: A systematic review.","authors":"Cristina Gallego-Fabrega, Natalia Cullell, Israel Fernández-Cadenas","doi":"10.1177/0271678X251322032","DOIUrl":"10.1177/0271678X251322032","url":null,"abstract":"The impact of DNA methylation (DNAm) on epigenetics has gained prominence in recent years due to its potential influence on ischemic stroke (IS) and treatment outcomes. DNAm is reversible and a better understanding of its role in IS could help identify novel therapeutic targets. The aim of this systematic review was to compile the available data on DNAm in the risk and prognosis of IS and to explore its therapeutic potential. The review process followed the PRISMA criteria. We searched the Pubmed and Cochrane databases to identify studies that used hypothesis free methodological approaches. Of the 459 studies identified, 34 met the inclusion criteria. The studies were categorized as follows: risk of IS; outcomes; and DNAm age. Most studies used genotyping array technology rather than whole-genome sequencing. DNAm testing was mainly based on blood samples. Most studies involved European cohorts. Most of the studies were performed at a single-center with recruitment at the time of stroke. In a few studies, health status was determined longitudinally. This systematic review shows that IS patients are biologically older than expected and present characteristic DNAm patterns related to stroke risk and outcomes. These patterns could be used to develop new treatments with epidrugs.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1369-1385"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515842","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}

引用次数: 0

Genetics of intracerebral hemorrhage. 脑出血的遗传学。

IF 4.7 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-06-01 Epub Date: 2025-01-07 DOI: 10.1177/0271678X241310401

Tamara N Kimball, Reinier Wp Tack, Anna Chen, Savvina Prapiadou, Jasper R Senff, Benjamin Yq Tan, Sanjula D Singh, Susanne J van Veluw, Steven M Greenberg, Jonathan Rosand, Christopher D Anderson

{"title":"Genetics of intracerebral hemorrhage.","authors":"Tamara N Kimball, Reinier Wp Tack, Anna Chen, Savvina Prapiadou, Jasper R Senff, Benjamin Yq Tan, Sanjula D Singh, Susanne J van Veluw, Steven M Greenberg, Jonathan Rosand, Christopher D Anderson","doi":"10.1177/0271678X241310401","DOIUrl":"10.1177/0271678X241310401","url":null,"abstract":"Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by heritability rates of up to 73% for lobar ICH versus 34% for non-lobar ICH. This review presents an outline of the genetic landscape of ICH, covering both monogenic and sporadic forms. It highlights associations between ICH risk and genetic variants, including rare and common variants in genes such as COL4A1, COL4A2, APOE, ACE, MTHFR, and PMF1. However, replication has been constrained, and most findings originate from single-candidate gene studies, largely due to ancestry heterogeneity, small sample sizes, and scarce subtype-specific data. To bridge this gap, collaborative efforts like the International Stroke Genetic Consortium have been established. Additionally, the review discusses the emerging role of polygenic risk scores, Mendelian randomization, and the potential of genetic and omics research to elucidate causal pathobiology. Such insights could lead to preventive measures and personalized ICH treatment strategies.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1324-1340"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122850","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}

引用次数: 0

Therapeutic mitochondria treatment amplifies macrophage-mediated phagocytosis and recycling exocytosis. 治疗性线粒体处理可扩大巨噬细胞介导的吞噬作用和循环外吞作用。

IF 4.5 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2026-02-01 Epub Date: 2025-03-13 DOI: 10.1177/0271678X251326871

Masayoshi Tanaka, Shin Ishikane, Dong Bin Back, Ester Licastro, Fang Zhang, Ji Hyun Park, Elga Esposito, Giuseppe Pignataro, Takafumi Nakano, Yoshihiko Nakamura, Kazuhide Hayakawa

{"title":"Therapeutic mitochondria treatment amplifies macrophage-mediated phagocytosis and recycling exocytosis.","authors":"Masayoshi Tanaka, Shin Ishikane, Dong Bin Back, Ester Licastro, Fang Zhang, Ji Hyun Park, Elga Esposito, Giuseppe Pignataro, Takafumi Nakano, Yoshihiko Nakamura, Kazuhide Hayakawa","doi":"10.1177/0271678X251326871","DOIUrl":"10.1177/0271678X251326871","url":null,"abstract":"Therapeutic administration of mitochondria has been increasingly explored. However, how these administered mitochondria impact immune response remains to be fully addressed. In this proof-of-concept study, we show that extracellularly added mitochondria to cultured peritoneal macrophages increase phagocytosis and recycling exocytosis that amplifies neuroplasticity mediated by recycled mitochondria transfer. Macrophage activation markers such as Nos2, Arg1, and Cd163 were unchanged at 3 h post-treatment with mitochondria, but whole mitochondria or delivery of mRNAs extracted from whole mitochondria appeared to increase SQSTM1 protein and activate Nrf2-mediated phagocytosis in macrophages, whereas mitochondria treatment did not change the ability of phagocytosis in cultured microglia or astrocytes. Notably, the once engulfed mitochondria in macrophages appear to be released via Rab27a-mediated recycling pathway that were favorably incorporated in mechanically damaged neurons compared with healthy neurons, resulting in accelerating neurite extension in damaged neurons in a direct co-culture model. Altogether, these findings uncover unappreciated mechanisms that mitochondria-treated macrophages upregulate phagocytosis and recycling exocytosis, implicating that engineering mitochondria delivery to macrophages is a new therapeutic intervention to promote neurorecovery in CNS disorders.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"406-417"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624829","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}

引用次数: 0