ArticleBlood2021
Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05585255 (Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury), which is not on this map. Cited by 139 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury
Who cites it
139 citing papers in PubMed, 213 citations in OpenAlex.
- Histone neutralization protects the ischemic brain against the consequences of stroke-associated pneumonia.Acta neuropathologica · 2026Article
- Neutrophil extracellular traps delivering lactylated S100a9 aggravate neuronal cuproptosis by regulating Ttr/Commd1/Atp7b axis after traumatic brain injury.Redox biology · 2026Article
- Systemic immune-inflammation index predicts hemorrhagic transformation after endovascular therapy for ischemic stroke.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- NET-mediated immunothrombosis in ischemic stroke: pathobiology, biomarkers, and therapeutic targeting.Thrombosis journal · 2026Review
- The NETs-cGAS-STING Axis in Ischemic Stroke: Linking Neutrophil-Microglia Crosstalk, Immunothrombosis, and Neuroinflammation.Molecular neurobiology · 2026Review
- [Mechanisms of cGAS-STING signaling pathway mediated neuroinflammation in central nervous system and their therapeutic implications].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Colchicine as an Adjunctive Therapy to Improve Ischemic Stroke Reperfusion Outcomes in Mice.CNS neuroscience & therapeutics · 2026Article
- Evolution of neutrophil extracellular traps in the pathology of stroke.Neural regeneration research · 2026Article
- Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Epigenetic Regulation of the NET Formation-Blood-Brain Barrier Axis in Ischemic Stroke: Mechanisms, Therapeutic Targets and Translational Perspectives.Neurology international · 2026Review
- GPNMB modulates neutrophil extracellular trap formation: therapeutic implications for ischemic stroke.Journal of neuroinflammation · 2026Article
- Engineered M2 macrophage-derived vesicles deliver DNase I for cfDNA clearance and multi-organ protection in sepsis.International journal of pharmaceutics: X · 2026Article
- Nrf2 regulates ICAM-1-mediated neutrophil extracellular trap formation after traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Integration of bioinformatics analysis and experimental verification reveals the role of neutrophil extracellular traps in silica nanoparticles-induced lung injury.Journal of nanobiotechnology · 2026Article
- Potential of intranasal delivery of human mesenchymal stem cells and extracellular vesicles for stroke therapy.Acta biomaterialia · 2026Review
- Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review).International journal of molecular medicine · 2026Review
- Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke.Fluids and barriers of the CNS · 2026Article
- Polymersomes preventing brain infiltration of CD177Nature communications · 2026Article
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracerebral hemorrhage associated with thrombolytic therapy with tissue plasminogen activator (tPA) in acute ischemic stroke continues to present a major clinical problem. Here, we report that infusion of tPA resulted in a significant increase in markers of neutrophil extracellular traps (NETs) in the ischemic cortex and plasma of mice subjected to photothrombotic middle cerebral artery occlusion. Peptidylarginine deiminase 4 (PAD4), a critical enzyme for NET formation, is also significantly upregulated in the ischemic brains of tPA-treated mice. Blood-brain barrier (BBB) disruption after ischemic challenge in an in vitro model of BBB was exacerbated after exposure to NETs. Importantly, disruption of NETs by DNase I or inhibition of NET production by PAD4 deficiency restored tPA-induced loss of BBB integrity and consequently decreased tPA-associated brain hemorrhage after ischemic stroke. Furthermore, either DNase I or PAD4 deficiency reversed tPA-mediated upregulation of the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). Administration of cGAMP after stroke abolished DNase I-mediated downregulation of the STING pathway and type 1 interferon production and blocked the antihemorrhagic effect of DNase I in tPA-treated mice. We also show that tPA-associated brain hemorrhage after ischemic stroke was significantly reduced in cGas-/- mice. Collectively, these findings demonstrate that NETs significantly contribute to tPA-induced BBB breakdown in the ischemic brain and suggest that targeting NETs or cGAS may ameliorate thrombolytic therapy for ischemic stroke by reducing tPA-associated hemorrhage.
Indexed as
Identifiers
What OpenQuestion holds
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.