ArticleArteriosclerosis, thrombosis, and vascular biology2024
Neutrophils and Neutrophil Extracellular Traps Cause Vascular Occlusion and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage in Mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 32 citations in OpenAlex.
- Haemorrhage, hypercoagulability and ischaemia: Evolution of brain injury after aneurysmal subarachnoid haemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Association of Inflammatory Markers With Symptomatic Intracranial Hemorrhage, Malignant Cerebral Edema, and Poor Functional Recovery in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy.Journal of the American Heart Association · 2026Article
- Evolution of neutrophil extracellular traps in the pathology of stroke.Neural regeneration research · 2026Article
- Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.Translational stroke research · 2026Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Microthrombi and hypercoagulability's contribution to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Predictive value of neutrophil-to-apolipoprotein A1 ratio for early postoperative cerebral infarction in patients with ruptured cerebral aneurysms.Lipids in health and disease · 2026Article
- Platelets cause microvascular occlusion and delayed neurological deficits after subarachnoid hemorrhage in mice.Experimental & molecular medicine · 2026Article
- The Perspective of Using Ischemic Tolerance in Clinical Practice.Biomedicines · 2026Review
- Aerobic Exercise-Induced TGF-β Receptor Reprogramming Disrupts Neutrophil-Microglia Crosstalk to Attenuate Early Brain Injury after Subarachnoid Hemorrhage.Research (Washington, D.C.) · 2026Article
- A NET-competent neutrophil subpopulation drives early brain injury after subarachnoid hemorrhage.Frontiers in neuroscience · 2026Article
- The role of glymphatic system in brain injury after subarachnoid hemorrhage.Frontiers in immunology · 2026Review
- Admission neutrophil-to-high-density lipoprotein cholesterol ratio and the risk of preoperative early rebleed in aneurysmal subarachnoid hemorrhage.European journal of medical research · 2025Article
- Early peripheral blood gene expression predicts 90-day outcomes following subarachnoid hemorrhage.Journal of neuroinflammation · 2025Article
- The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Review
- Distinct immune-metabolic phenotypes underlie poor coronary collateral circulation.Cardiovascular diabetology · 2025Article
- Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Patients With Subarachnoid Hemorrhage.Journal of the American Heart Association · 2025Article
- Neutrophil Integrin α9 Impairs Efferocytosis and Worsens Long-Term Recovery After Subarachnoid Hemorrhage.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4.Translational stroke research · 2025Article
- Neutrophils-astrocyte interactions in central nervous system inflammation.Cell death & disease · 2025Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAfter subarachnoid hemorrhage (SAH), neutrophils are deleterious and contribute to poor outcomes. Neutrophils can produce neutrophil extracellular traps (NETs) after ischemic stroke. Our hypothesis was that, after SAH, neutrophils contribute to delayed cerebral ischemia (DCI) and worse outcomes via cerebrovascular occlusion by NETs.
methodsSAH was induced via endovascular perforation, and SAH mice were given either a neutrophil-depleting antibody, a PAD4 (peptidylarginine deiminase 4) inhibitor (to prevent NETosis), DNAse-I (to degrade NETs), or a vehicle control. Mice underwent daily neurological assessment until day 7 and then euthanized for quantification of intravascular brain NETs (iNETs). Subsets of mice were used to quantify neutrophil infiltration, NETosis potential, iNETs, cerebral perfusion, and infarction. In addition, NET markers were assessed in the blood of aneurysmal SAH patients.
resultsIn mice, SAH led to brain neutrophil infiltration within 24 hours, induced a pro-NETosis phenotype selectively in skull neutrophils, and caused a significant increase in iNETs by day 1, which persisted until at least day 7. Neutrophil depletion significantly reduced iNETs, improving cerebral perfusion, leading to less neurological deficits and less incidence of DCI (16% versus 51.9%). Similarly, PAD4 inhibition reduced iNETs, improved neurological outcome, and reduced incidence of DCI (5% versus 30%), whereas degrading NETs marginally improved outcomes. Patients with aneurysmal SAH who developed DCI had elevated markers of NETs compared with non-DCI patients.
conclusionsAfter SAH, skull-derived neutrophils are primed for NETosis, and there are persistent brain iNETs, which correlated with delayed deficits. The findings from this study suggest that, after SAH, neutrophils and NETosis are therapeutic targets, which can prevent vascular occlusion by NETs in the brain, thereby lessening the risk of DCI. Finally, NET markers may be biomarkers, which can predict which patients with aneurysmal SAH are at risk for developing DCI.
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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 Socratic graph.