ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 2 of them syntheses that pooled it.
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Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.Scientific reports · 2016Pooled it
- Gq Signaling in Microglia Triggers Interferon Responses and Improves Outcome After Ischemic Stroke.Glia · 2026Article
- Interferon regulatory factors: the next prospective targets for tissue ischemia-reperfusion injury?Frontiers in immunology · 2026Review
- Resveratrol mitigated acute sleep deprivation-induced cognitive impairment by suppressing hippocampal neuronal ferroptosis.3 Biotech · 2025Article
- Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials.Translational stroke research · 2025Review
- Remote Preconditioning Provides Protection Against Retinal Cell Death From Retinal Detachment.Investigative ophthalmology & visual science · 2025Article
- Repeated LPS induces training and tolerance of microglial responses across brain regions.Journal of neuroinflammation · 2024Article
- Effectiveness of remote ischaemic conditioning is not affected by hyper-inflammation in a rat model of stroke.Scientific reports · 2024Article
- Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury.Frontiers in immunology · 2024Article
- Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post stroke.Journal of biomedical science · 2023Article
- Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice.Genes & diseases · 2023Article
- Toll-like receptors in pathogenesis of neurodegenerative diseases and their therapeutic potential.Immunity, inflammation and disease · 2023Review
- Cortex-specific transcriptome profiling reveals upregulation of interferon-regulated genes after deeper cerebral hypoperfusion in mice.Frontiers in physiology · 2023Article
- Interferon-β modulates microglial polarization to ameliorate delayed tPA-exacerbated brain injury in ischemic stroke.Frontiers in immunology · 2023Article
- Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2022Review
- Remote ischemic conditioning causes CD4 T cells shift towards reduced cell-mediated inflammation.Pediatric surgery international · 2022Article
- Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice.Journal of neuroinflammation · 2022Article
- A Review of Neuroprotective Effects and Mechanisms of Ginsenosides From Panax Ginseng in Treating Ischemic Stroke.Frontiers in pharmacology · 2022Review
- Resveratrol reduces inflammatory response and detrimental effects in chronic cerebral hypoperfusion by down-regulating stimulator of interferon genes/TANK-binding kinase 1/interferon regulatory factor 3 signaling.Frontiers in aging neuroscience · 2022Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury through activation of its receptor, Toll-like receptor 4 (TLR4). Paradoxically, TLR activation by endogenous ligands after ischemia worsens stroke damage. Here, we define a novel, protective role for TLRs after ischemia in the context of LPS preconditioning. Microarray analysis of brains collected 24 h after stroke revealed a unique set of upregulated genes in LPS-pretreated animals. Promoter analysis of the unique gene set identified an overrepresentation of type I interferon (IFN)-associated transcriptional regulatory elements. This finding suggested the presence of type I IFNs or interferon regulatory factors (IRFs), which upregulate interferon-stimulated genes. Upregulation of IFNbeta was confirmed by real-time reverse transcription-PCR. Direct administration of IFNbeta intracerebroventricularly at the time of stroke was sufficient for neuroprotection. TLR4 can induce both IFNbeta and interferon-stimulated genes through its adapter molecule Toll/interleukin receptor domain-containing adaptor-inducing IFNbeta (TRIF) and the IRF3 transcription factor. We show in oxygen glucose deprivation of cortical neurons, an in vitro model of stroke, that activation of TRIF after stroke reduces neuronal death. Furthermore, mice lacking IRF3 were not protected by LPS preconditioning in our in vivo model. Our studies constitute the first demonstration of the neuroprotective capacity of TRIF/IRF3 signaling and suggest that interferon-stimulated genes, whether induced by IFNbeta or by enhanced TLR signaling to IRF3, are a potent means of protecting the brain against ischemic damage.
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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.