ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through release of proteases associated with decondensed DNA.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
159 citing papers in PubMed, 2 syntheses or guidelines pooled it, 232 citations in OpenAlex.
- Neutrophil extracellular traps correlate with severity and prognosis in patients with ischemic stroke: a systematic review and meta-analysis.Acta neurologica Belgica · 2024Pooled it
- A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury.Frontiers in immunology · 2022Pooled it
- JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.Journal of leukocyte biology · 2015Trial
- Type I IFN coordinates resistance and tolerance against Zika virus disease by inducing NK cell recruitment and limiting neutrophil-driven neuropathology in the brain.Brain, behavior, & immunity - health · 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
- Microglia and border-associated macrophages play opposite roles in cerebrovascular and leukocyte responses under systemic inflammation in male mice.Nature communications · 2026Article
- Neutrophil-targeted nanoparticles delivering sivelestat alleviate cerebral ischemia-reperfusion injury by suppressing NETosis.Materials today. Bio · 2026Article
- The Association Between PIV and Mortality in US Stroke Survivors: A NHANES 1999-2018 Retrospective Cohort Study.Health science reports · 2026Article
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Serum ferritin, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio are associated with levodopa-induced dyskinesia severity in Parkinson's disease.BMC neurology · 2026Article
- Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis.Biochemistry and biophysics reports · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Neutrophil-to-albumin ratio and all-cause mortality in critically ill patients with cerebral infarction: a retrospective cohort study using the MIMIC-IV database.European journal of medical research · 2026Article
- Mechanistic insights into the synaptic damage-repair and regeneration processes in neurodegenerative Alzheimer's disease: phytochemicals as neuroprotective agents.Frontiers in synaptic neuroscience · 2026Review
- The cell-mediated adaptive immune response to herpes simplex virus type 1 encephalitis: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- Bradykinin Type 2 Receptor Deficiency Reshapes Acute Neuroinflammation and Improves Cell Survival after Ischemic Stroke in Diabetic Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- The impact of PANoptosis-related genes on immune profiles and subtype classification in ischemic stroke.Scientific reports · 2025Article
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Article
- Photoreceptor loss does not recruit neutrophils despite strong microglial activation.bioRxiv : the preprint server for biology · 2025Article
99 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Cerebrovascular inflammation contributes to diverse CNS disorders through mechanisms that are incompletely understood. The recruitment of neutrophils to the brain can contribute to neurotoxicity, particularly during acute brain injuries, such as cerebral ischemia, trauma, and seizures. However, the regulatory and effector mechanisms that underlie neutrophil-mediated neurotoxicity are poorly understood. In this study, we show that mouse neutrophils are not inherently toxic to neurons but that transendothelial migration across IL-1-stimulated brain endothelium triggers neutrophils to acquire a neurotoxic phenotype that causes the rapid death of cultured neurons. Neurotoxicity was induced by the addition of transmigrated neutrophils or conditioned medium, taken from transmigrated neutrophils, to neurons and was partially mediated by excitotoxic mechanisms and soluble proteins. Transmigrated neutrophils also released decondensed DNA associated with proteases, which are known as neutrophil extracellular traps. The blockade of histone-DNA complexes attenuated transmigrated neutrophil-induced neuronal death, whereas the inhibition of key neutrophil proteases in the presence of transmigrated neutrophils rescued neuronal viability. We also show that neutrophil recruitment in the brain is IL-1 dependent, and release of proteases and decondensed DNA from recruited neutrophils in the brain occurs in several in vivo experimental models of neuroinflammation. These data reveal new regulatory and effector mechanisms of neutrophil-mediated neurotoxicity (i.e., the release of proteases and decondensed DNA triggered by phenotypic transformation during cerebrovascular transmigration). Such mechanisms have important implications for neuroinflammatory disorders, notably in the development of antileukocyte therapies.
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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.