ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 papers, 2 of them syntheses that pooled it.
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Who cites it
261 citing papers in PubMed, 2 syntheses or guidelines pooled it, 682 citations in OpenAlex.
- Therapeutic potential of nitric oxide and its donors in hemorrhagic and ischemic stroke: a systematic review.Medical gas research · 2026Pooled it
- Neuroinflammation: A Common Pathway in Alzheimer's Disease and Epilepsy.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Astrocyte Functional Heterogeneity in Multiple Sclerosis.Journal of clinical neurology (Seoul, Korea) · 2026Review
- Exploring the Research Progress of Vascular Dementia and Key Regulatory Molecules: E2F1.International journal of molecular sciences · 2026Review
- HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview.International journal of molecular sciences · 2026Review
- Effects of Exogenous SARS-CoV-2 S1 Protein and mRNA Vaccines on Mixed Neuronal-Glial Cell Cultures.Medicina (Kaunas, Lithuania) · 2026Article
- A Case of Bilateral Globus Pallidus Infarction Onset With Mental Disorder.Case reports in neurological medicine · 2026Article
- Investigating the Antioxidant, Pro-Inflammatory Enzyme Inhibitory, Neuroprotective, and Antineuroinflammatory Bioactives ofACS omega · 2025Article
- Novel neurotherapeutic targets for substance use disorders: Neuroplasticity, neuroinflammation, gasotransmitters and non-canonical organ systems.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Imaging markers of neuroinflammation in aging and Alzheimer's disease and related dementia: A comprehensive review.Neuroscience and biobehavioral reviews · 2025Review
- From Acute Injury to Chronic Neurodegeneration: Molecular Mechanisms Linking Secondary Brain Injury to Long-Term Pathology.International journal of molecular sciences · 2025Review
- From the different pathogenesis of epileptogenesis: vitamins as an adjunctive treatment for epilepsy.Acta epileptologica · 2025Review
- Anti-Inflammatory Effects of Honeysuckle Leaf Against Lipopolysaccharide-Induced Neuroinflammation on BV2 Microglia.Nutrients · 2024Article
- Retinoic acid-induced differentiation and oxidative stress inhibitors increase resistance of human neuroblastoma cells to La Crosse virus-induced cell death.Journal of virology · 2024Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain.Biomolecules & biomedicine · 2024Article
- Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.Scientific reports · 2024Article
- Basic Science of Neuroinflammation and Involvement of the Inflammatory Response in Disorders of the Nervous System.Magnetic resonance imaging clinics of North America · 2024Review
- JAK1/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Disease phenotypic screening in neuron-glia cocultures identifies blockers of inflammatory neurodegeneration.iScience · 2024Article
201 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glia undergo inflammatory activation in most CNS pathologies and are capable of killing cocultured neurons. We investigated the mechanisms of this inflammatory neurodegeneration using a mixed culture of neurons, microglia, and astrocytes, either when the astrocytes were activated directly with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) or LPS/IFN-gamma-activated microglia were added to mixed neuronal cultures. In either case, activated glia caused 75-100% necrotic cell death within 48 hr, which was completely prevented by inhibitors of inducible nitric oxide synthase (iNOS) (aminoguanidine or 1400W). Activated astrocytes or microglia produced nitric oxide (NO) (steady-state level approximately 0.5 microm), which immediately inhibited the cellular respiration of cocultured neurons, as did authentic NO. NO donors also decreased ATP levels and stimulated lactate production by neurons, consistent with NO-induced respiratory inhibition. NO donors or a specific respiratory inhibitor caused rapid (<1 min) release of glutamate from neuronal and neuronal-astrocytic cultures and subsequent neuronal death that was blocked by an antagonist of NMDA receptor (MK-801). MK-801 also blocked neuronal death induced by activated glia. High oxygen also prevented NO-induced neuronal death, consistent with death being induced by NO inhibition of cytochrome c oxidation in competition with oxygen. Thus activated glia kill neurons via NO from iNOS, which inhibits neuronal respiration resulting in glutamate release and subsequent excitotoxicity. This may contribute to neuronal cell death in inflammatory, infectious, ischemic, and neurodegenerative diseases.
Indexed as
Identifiers
11517237PMC6763071W1668344921What 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.