ArticleBlood2020
Platelet necrosis mediates ischemic stroke outcome in mice.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association of the systemic immune-inflammation index (SII) and clinical outcomes in patients with stroke: A systematic review and meta-analysis.Frontiers in immunology · 2022Pooled it
- Platelet Cyclophilin D Drives Cholesterol Crystal Embolism-Related Acute Kidney Injury and Kidney Infarction.Journal of the American Society of Nephrology : JASN · 2026Article
- Procoagulant platelets: linking coagulation and thromboinflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.Translational stroke research · 2026Review
- Inflammation and wound healing: a comprehensive overview of mechanisms, therapeutic strategies, and translational perspectives.Biomarker research · 2026Review
- Platelet mTOR Is a Regulator of Sterile Immunothrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Heme and hemozoin induce platelet cell death through UPR-induced apoptosis and ferroptosis in vivax malaria.Blood advances · 2026Article
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Complete blood count-derived inflammatory markers in canine cerebrovascular accidents: diagnostic utility and prognostic implications.Frontiers in veterinary science · 2026Article
- Advanced radiomics techniques applied on carotid duplex ultrasound data predict adverse outcomes in acute ischemic stroke.Frontiers in neurology · 2026Article
- Neutrophil extracellular traps-targeting therapy with deoxyribonuclease 1 reduces large vessel occlusion-induced downstream microvascular thromboinflammation in a rat model of stroke.Research and practice in thrombosis and haemostasis · 2025Article
- Immunological Mechanisms and Therapeutic Strategies in Cerebral Ischemia-Reperfusion Injury: From Inflammatory Response to Neurorepair.International journal of molecular sciences · 2025Review
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- Converging Molecular Mechanisms of Nucleated Cell Death Pathways and Procoagulant Platelet Formation.Cells · 2025Review
- An orally administered gene editing nanoparticle boosts chemo-immunotherapy in colorectal cancer.Nature nanotechnology · 2025Article
- Theaflavin-3,3'-digallate protects against myocardial ischemia/reperfusion injury and hypoxia/reoxygenation injury by activating the PI3K/Akt/mTOR pathway.Journal of molecular histology · 2025Article
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Platelet spleen tyrosine kinase is a key regulator of anti-PF4 antibody-induced immunothrombosis.Blood advances · 2025Article
- Article
- Mice with reduced protease-activated receptor 4 reactivity show decreased venous thrombosis and platelet procoagulant activity.Journal of thrombosis and haemostasis : JTH · 2025Article
8 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Dysregulated platelet functions contribute to the development and progression of ischemic stroke. Utilizing mice with a platelet-specific deletion of cyclophilin D (CypD), a mediator of necrosis, we found that platelet necrosis regulates tissue damage and outcomes during ischemic stroke in vivo. Mice with loss of CypD in platelets (CypDplt-/-mice) exhibited significantly enhanced cerebral blood flow, improved neurological and motor functions, and reduced ischemic stroke infarct volume after cerebral ischemia-reperfusion injury. These effects were attributable, at least in part, to platelet-neutrophil interactions. Twenty-four hours after stroke, significantly more circulating platelet-neutrophil aggregates (PNAs) were found in CypDplt+/+ mice. Underscoring the role of platelet necrosis in PNA formation, we observed a significant number of phosphatidylserine (PS)+ platelets in PNAs in CypDplt+/+ mice. In contrast, significantly fewer platelets in PNAs were PS+ in CypDplt-/- counterparts. Accordingly, mice with CypD-deficient platelets had fewer neutrophils and PNAs recruited to their brain following stroke relative to wild-type counterparts. Neutrophil depletion in wild-type mice conferred protection from ischemic stroke to a similar degree as observed in mice with CypD-deficient platelets. Neutrophil depletion in CypDplt-/- mice did not further reduce infarct size. Transmission electron microscopy of ex vivo-formed PNAs revealed a propensity of necrotic platelets to interact with neutrophils. These results suggest that necrotic platelets interact with neutrophils to exacerbate brain injury during ischemic stroke. Because inhibiting platelet necrosis does not compromise hemostasis, targeting platelet CypD may be a potential therapeutic strategy to limit brain damage following 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.