ArticleCell death & disease2019
Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07176754 (TNF-a Antagonists Attenuate the Systemic Inflammatory Response in Post-cardiac Arrest Syndrome), which is not on this map. Cited by 310 papers, 2 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.
TNF-a Antagonists Attenuate the Systemic Inflammatory Response in Post-cardiac Arrest Syndrome: a Multi Centre, Double-blind, Randomised Controlled Clinical Study
Who cites it
310 citing papers in PubMed, 2 syntheses or guidelines pooled it, 544 citations in OpenAlex.
- Microglial Responses to MSC-EVs Treatment in Animal and Cellular Models of Ischemic Stroke: a Systematic Review with Meta-analysis.Molecular neurobiology · 2025Pooled it
- Role and Mechanism of Microglia in White Matter Injury Recovery in Ischemic Stroke.Immunity, inflammation and disease · 2025Pooled it
- The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation.Physiology (Bethesda, Md.) · 2026Review
- Pre-Treatment Levels of Inflammatory Biomarkers as Predictors of Reperfusion Outcomes in Acute Ischemic Stroke: A Systematic Review and Meta-analysis.Neurology and therapy · 2026Review
- Nano Proton Scavengers Modulate Endosomal pH to Inhibit Microglial Activation and Enhance Stroke Recovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein-protein interaction-mediated signaling networks in ischemic stroke: from molecular mechanisms to therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Blockade of the SP/NK1 receptor axis: multimodal neuroprotection via inflammatory suppression, hypoxic modulation, and lympho-vascular remodeling in global cerebral ischemia.Metabolic brain disease · 2026Article
- Evaluation of modafinil's neuroprotective effects in lipopolysaccharide-induced sepsis-associated encephalopathy: associations with GSK3β, inflammatory, oxidative stress, and apoptotic signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Gut-brain axis modulation by fecal microbiota transplantation improves dual-organ injury after cerebral ischemia-reperfusion via Caspase-8 dependent inhibition of necroptosis.Metabolic brain disease · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Total flavones of Rhododendron protect against BBB injury following cerebral ischemia/reperfusion via promoting astrocytic polarization towards A2 subtype.Apoptosis : an international journal on programmed cell death · 2026Article
- The CEBPB-AP-1 (JunB/Fos) Axis Drives Neuroinflammation and Microglial Dysfunction Via TNF Signaling in Ischemic Stroke.Inflammation · 2026Article
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- Zhi-Zi-Chi Decoction Alleviates Depressive-like Behaviors by Regulating Gut Microbiota and Targeting the AMPK/PI3K-TOR Pathway via Its Metabolite Protocatechuic Acid.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Hydrogen Sulfide Protects Against Cerebral Ischemia-Reperfusion Injury in Rats via S-Sulfhydrating NAMPT to Enhance Mitochondrial Function and Autophagy in Cerebrovascular Endothelial Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The role of DAP12 in immune-related inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Vessel-associated microglia are differentially activated and distributed in relation to systemic infection and Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Extracellular vesicles: Revolutionizing targeted therapy for ischemic stroke.Acta pharmaceutica Sinica. B · 2026Review
- The Degree of Liver Steatosis Is Associated with Abnormally High Serum Levels of Markers of Blood-Brain Barrier Dysfunction and Systemic Inflammation in Patients with Morbid Obesity.Medicina (Kaunas, Lithuania) · 2026Article
250 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microglia-induced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFα (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug 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.