ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Endogenous nitric oxide is a key promoting factor for initiation of seizure-like events in hippocampal and entorhinal cortex slices.
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 44 papers.
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Who cites it
44 citing papers in PubMed, 107 citations in OpenAlex.
- Candidate Serum Biomarkers of Neural Injury and Neuroinflammation in Childhood Epilepsy: Comparison Between Controlled and Drug-Resistant Phenotypes.Children (Basel, Switzerland) · 2026Article
- Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy.Histology and histopathology · 2026Review
- Cytoprotective and Immunomodulatory Properties of Mesenchymal Stem Cell Secretome and Its Effect on Organotypic Hippocampal Cultures in Mouse Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2025Article
- The nitrergic mechanism of geraniol in PTZ-induced seizures.IBRO neuroscience reports · 2025Article
- Exploration of Canarium odontophyllum fruit phytoconstituents as potential candidates against epilepsy using in silico studies.Journal, genetic engineering & biotechnology · 2025Article
- Unveiling the hidden connection: the blood-brain barrier's role in epilepsy.Frontiers in neurology · 2024Review
- Article
- Neuronal nitric oxide synthase/reactive oxygen species pathway is involved in apoptosis and pyroptosis in epilepsy.Neural regeneration research · 2023Article
- Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement.Iranian journal of medical sciences · 2023Article
- 2-AG-Mediated Control of GABAergic Signaling Is Impaired in a Model of Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines.Nature communications · 2021Article
- The role of nitric oxide in anticonvulsant effects of lycopene supplementation on pentylenetetrazole-induced epileptic seizures in rats.Experimental brain research · 2021Article
- Negative Feedback Role of Astrocytes in Shaping Excitation in Brain Cell Co-cultures.Frontiers in cellular neuroscience · 2021Article
- Neurochemical effects of sleep deprivation in the hippocampus of the pilocarpine-induced rat model of epilepsy.Iranian journal of basic medical sciences · 2021Article
- Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy.Journal of neuroscience research · 2019Review
- Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management.Journal of neuroinflammation · 2019Review
- Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery.IEEE transactions on bio-medical engineering · 2019Article
- Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Pathology of nNOS-Expressing GABAergic Neurons in Mouse Model of Alzheimer's Disease.Neuroscience · 2018Article
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO) modulates synaptic transmission, and its level is elevated during epileptic activity in animal models of epilepsy. However, the role of NO for development and maintenance of epileptic activity is controversial. We studied this aspect in rat organotypic hippocampal slice cultures and acute hippocampal-entorhinal cortex slices from wild-type and neuronal NO synthase (nNOS) knock-out mice combining electrophysiological and fluorescence imaging techniques. Slice cultures contained nNOS-positive neurons and an elaborated network of nNOS-positive fibers. Lowering of extracellular Mg(2+) concentration led to development of epileptiform activity and increased NO formation as revealed by NO-selective probes, 4-amino-5-methylamino-2',7'-difluorofluorescein and 1,2-diaminoanthraquinone sulfate. NO deprivation by NOS inhibitors and NO scavengers caused depression of both EPSCs and IPSCs and prevented initiation of seizure-like events (SLEs) in 75% of slice cultures and 100% of hippocampal-entorhinal cortex slices. This effect was independent of the guanylyl cyclase/cGMP pathway. Suppression of SLE initiation in acute slices from mice was achieved by both the broad-spectrum NOS inhibitor N-methyl-L-arginine acetate and the nNOS-selective inhibitor 7-nitroindazole, whereas inhibition of inducible NOS by aminoguanidine was ineffective, suggesting that nNOS activity was crucial for SLE initiation. Additional evidence was obtained from knock-out animals because SLEs developed in a significantly lower percentage of slices from nNOS(-/-) mice and showed different characteristics, such as prolongation of onset latency and higher variability of SLE intervals. We conclude that enhancement of synaptic transmission by NO under epileptic conditions represents a positive feedback mechanism for the initiation of seizure-like events.
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