ArticleThe Journal of clinical investigation2022
Neutrophil extracellular traps regulate ischemic stroke brain injury.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
239 citing papers in PubMed, 6 syntheses or guidelines pooled it, 322 citations in OpenAlex.
- Diagnostic accuracy of circulating blood biomarker families in acute ischemic stroke: a secondary grouped meta-analysis with primary-study verification.Frontiers in neurology · 2026Pooled it
- Histological Insights into the Neuroprotective Effects of Antioxidant Peptides and Small Molecules in Cerebral Ischemia.Molecules (Basel, Switzerland) · 2025Pooled it
- Investigating the Role of Neutrophil Extracellular Traps as a Therapeutic Target in Traumatic Brain Injury: a Systematic Review and Meta-analysis.Molecular neurobiology · 2025Pooled it
- Research trends on neutrophil extracellular traps in ischemic stroke: a scientific metrology study.Frontiers in pharmacology · 2025Pooled it
- Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence.Cells · 2024Pooled it
- Systemic inflammation response index as a clinical outcome evaluating tool and prognostic indicator for hospitalized stroke patients: a systematic review and meta-analysis.European journal of medical research · 2023Pooled it
- Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?Translational stroke research · 2025Trial
- Relationship Between Neutrophil Count and 90-Day Outcomes and Effect of Dual Antiplatelet Therapy in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the INSPIRES Trial.Journal of the American Heart Association · 2025Trial
- Histone neutralization protects the ischemic brain against the consequences of stroke-associated pneumonia.Acta neuropathologica · 2026Article
- Hyperacute Interleukin-1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion.Annals of neurology · 2026Article
- Intercellular communication between peripheral monocytes and central nervous system cells in stroke.Neural regeneration research · 2026Article
- Review
- Beyond Recanalization: Neurovascular Unit Protection and Precision Adjunctive Therapy for Ischemic Stroke in the Reperfusion Era.Biomolecules · 2026Review
- Stent retrievers for acute ischemic stroke: technological advances, clinical applications, and future perspectives.Journal of neurology · 2026Review
- Surgical protocol and ischemic duration determine myeloid cell features and locomotor deficits in preclinical transient middle cerebral artery occlusion.Experimental neurology · 2026Article
- Review
- Emerging evidence of neutrophil extracellular traps in essential hypertension and target organ damage: pathophysiological insights and therapeutic implications.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- NET-mediated immunothrombosis in ischemic stroke: pathobiology, biomarkers, and therapeutic targeting.Thrombosis journal · 2026Review
- Neutrophil-targeted nanoparticles delivering sivelestat alleviate cerebral ischemia-reperfusion injury by suppressing NETosis.Materials today. Bio · 2026Article
179 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.
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Registered trials
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.