ArticleJournal of thrombosis and haemostasis : JTH2021
Hyperglycemia exacerbates ischemic stroke outcome independent of platelet glucose uptake.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Platelet homeostasis and heterogeneity in inflammation and sepsis: mechanisms, biological effects, and clinical potential.Cell communication and signaling : CCS · 2026Review
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Platelet mTOR Is a Regulator of Sterile Immunothrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Sodium-Glucose Cotransporter 2 Inhibitors: An Emerging Therapeutic Approach for Ischemic Stroke Management.CNS drugs · 2025Review
- Joint impact of stress hyperglycaemic ratio and glycaemic variability in patients with ischaemic stroke and machine learning for mortality prediction.BMC neurology · 2025Article
- Stress Hyperglycemia as a Prognostic Indicator of the Clinical Outcomes in Patients with Stroke: A Comprehensive Literature Review.Biomedicines · 2025Review
- Exploring stroke risk factors in different genders using Bayesian networks: a cross-sectional study involving a population of 134,382.BMC public health · 2025Article
- Potential Predictive Value of Platelet Distribution Width for Functional Outcome After Ischemic Stroke.Molecular neurobiology · 2025Article
- Associations between stress hyperglycemia and outcomes in patients with ischemic stroke and TIA: the data comes from the Third China National Stroke Registry (CNSR-III).Metabolic brain disease · 2025Article
- The Association of Systemic Inflammatory Response Index and Neutrophil-to-High-Density Lipoprotein Ratio Mediated by Fasting Blood Glucose with 90-Day Prognosis in Acute Ischemic Stroke Patients.Neuroepidemiology · 2025Observational
- The persistent challenge of ischemic stroke burden from high fasting plasma glucose: a global perspective.Frontiers in endocrinology · 2025Article
- Cardiometabolic index predicts cardiovascular events in aging population: a machine learning-based risk prediction framework from a large-scale longitudinal study.Frontiers in endocrinology · 2025Article
- Association between blood glucose level trajectories and 30-day mortality risk in patients with acute ischemic stroke: analysis of the MIMIC database 2001-2019.Diabetology & metabolic syndrome · 2024Article
- Machine learning-based predictive model for the development of thrombolysis resistance in patients with acute ischemic stroke.BMC neurology · 2024Article
- Plant-derived compounds normalize platelet bioenergetics and function in hyperglycemia.Research and practice in thrombosis and haemostasis · 2024Article
- Immunothrombosis in neurovascular disease.Research and practice in thrombosis and haemostasis · 2024Article
- Causal relationship between novel antidiabetic drugs and ischemic stroke: a drug-targeted Mendelian randomization study.Frontiers in cardiovascular medicine · 2024Article
- Serum Glucose-Phosphate Ratio on Admission as a Potential Biomarker for Severity, Functional Outcome, and Recurrence in Acute Ischemic Stroke.International journal of general medicine · 2024Article
- Natural Fatty Acid Guards against Brain Endothelial Cell Death and Microvascular Pathology following Ischemic Insult in the Presence of Acute Hyperglycemia.Biomedicines · 2023Article
- The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.The Journal of clinical investigation · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHyperglycemia is a common comorbidity for ischemic stroke and is associated with worsened neurological outcomes. Platelets are central mediators of ischemic stroke and hyperglycemia mediates platelet hyperactivity. In this study, we investigated the contribution of platelet glucose metabolism to ischemic stroke.
methodsMice lacking both Glut1 and Glut3 specifically in platelets (DKO) and their littermate controls (WT) were subjected to 1-hour transient middle cerebral artery occlusion under normoglycemic and streptozotocin-induced hyperglycemic conditions after which stroke outcomes, platelet activation, and platelet-neutrophil aggregate (PNA) formation were examined.
resultsUnder normoglycemic conditions, DKO mice were protected from ischemic stroke with smaller brain infarct volumes and improved cerebral blood flow. In addition, DKO mice had reduced platelet activation, PNA, and cerebral neutrophil recruitment after stroke. Hyperglycemia significantly increased infarct size and cerebral Evans blue extravasation and worsened neurological outcomes and cerebral blood flow in both WT and DKO mice, abolishing the protective effect witnessed under normoglycemic conditions. Flow cytometric analysis after stroke demonstrated increased platelet activation and neutrophil trafficking to the brain, independent of platelet glucose metabolism. Finally, platelets from healthy DKO mice were unable to become procoagulant upon dual agonist stimulation. Conversely, hyperglycemia increased platelet mitochondrial reactive oxygen species production which potentiated procoagulant platelet formation in WT mice and restored procoagulant platelet formation in DKO mice.
conclusionHyperglycemia aggravates ischemic stroke outcome independent of platelet glucose uptake. Furthermore, we demonstrated that hyperglycemia primes procoagulant platelet formation. This underlines the therapeutic potential for strategies targeting procoagulant platelet formation for the treatment of acute ischemic stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.