ArticlePloS one2013
Notch-1 signaling regulates microglia activation via NF-κB pathway after hypoxic exposure in vivo and in vitro.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 114 citations in OpenAlex.
- Notch Signaling in Spinal Cord Injury: Mechanistic Insights and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- Jojoba Oil Protects against Chlorpyrifos-Induced Testicular Toxicity by Modulating Notch1/Jagged1-Inflammatory Axis and Oxidative Stress.Cell biochemistry and biophysics · 2026Article
- Imiquimod enhances anti-tumor effects of CD47 targeting in oral squamous cell carcinoma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.Acta neuropathologica communications · 2026Article
- Folic acid modulates the Notch1/NF-κB pathway in a rat model of lipopolysaccharide-activated hippocampal microglia.Frontiers in neuroanatomy · 2026Article
- Antidepressant-Like Effects of Electroacupuncture by Regulating NLRP3-mediated Hippocampal Inflammation and Pyroptosis in Rats With Post-Stroke Depression.Brain and behavior · 2025Article
- Melatonin ameliorates astrogliosis and microgliosis in a cuprizone demyelinating mouse model.Biochemistry and biophysics reports · 2025Article
- Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation.Frontiers in aging neuroscience · 2025Article
- The role of growth hormone in assisted reproductive technology for patients with diminished ovarian reserve: from signaling pathways to clinical applications.Frontiers in endocrinology · 2025Review
- Single-cell transcriptomics of vascularized human brain organoids decipher lineage-specific stress adaptation in fetal hypoxia-reoxygenation injury.Theranostics · 2025Article
- Microglia in radiation-induced brain injury: Cellular and molecular mechanisms and therapeutic potential.CNS neuroscience & therapeutics · 2024Review
- Review
- Receptors on Microglia.Advances in neurobiology · 2024Review
- Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosisFrontiers in immunology · 2024Article
- Role of Microglial Modulation in Therapies for Perinatal Brain Injuries Leading to Neurodevelopmental Disorders.Advances in neurobiology · 2024Review
- Thoracic Spinal Cord Neuroinflammation as a Novel Therapeutic Target in Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Studies on the mechanism of Toxoplasma gondii Chinese 1 genotype Wh6 strain causing mice abnormal cognitive behavior.Parasites & vectors · 2023Article
- Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds.Frontiers in immunology · 2023Review
- Gastrodin Attenuates Lipopolysaccharide-Induced Inflammatory Response and Migration via the Notch-1 Signaling Pathway in Activated Microglia.Neuromolecular medicine · 2022Article
- Quercetin ameliorates lipopolysaccharide-induced neuroinflammation and oxidative stress in adult zebrafish.Molecular biology reports · 2022Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation mediated by the activated microglia is suggested to play a pivotal role in the pathogenesis of hypoxic brain injury; however, the underlying mechanism of microglia activation remains unclear. Here, we show that the canonical Notch signaling orchestrates microglia activation after hypoxic exposure which is closely associated with multiple pathological situations of the brain. Notch-1 and Delta-1 expression in primary microglia and BV-2 microglial cells was significantly elevated after hypoxia. Hypoxia-induced activation of Notch signaling was further confirmed by the concomitant increase in the expression and translocation of intracellular Notch receptor domain (NICD), together with RBP-Jκ and target gene Hes-1 expression. Chemical inhibition of Notch signaling with N-[N-(3,5-difluorophenacetyl)-1-alany1- S-phenyglycine t-butyl ester (DAPT), a γ-secretase inhibitor, effectively reduced hypoxia-induced upregulated expression of most inflammatory mediators. Notch inhibition also reduced NF-κB/p65 expression and translocation. Remarkably, Notch inhibition suppressed expression of TLR4/MyD88/TRAF6 pathways. In vivo, Notch signaling expression and activation in microglia were observed in the cerebrum of postnatal rats after hypoxic injury. Most interestingly, hypoxia-induced upregulation of NF-κB immunoexpression in microglia was prevented when the rats were given DAPT pretreatment underscoring the interrelationship between Notch signaling and NF-κB pathways. Taken together, we conclude that Notch signaling is involved in regulating microglia activation after hypoxia partly through the cross talk between TLR4/MyD88/TRAF6/NF-κB pathways. Therefore, Notch signaling may serve as a prospective target for inhibition of microglia activation known to be implicated in brain damage in the developing brain.
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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.