ArticlePloS one2013
Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively modulate GABA mediated neurotransmission to delay onset of seizures.
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 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery.Journal of lipid research · 2016Trial
- The Roles of EETs in Neurological Disorders.CNS neuroscience & therapeutics · 2026Review
- Inhibition of Soluble Epoxide Hydrolase Prevents Docetaxel-Induced Painful Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- A Narrative Review of the Published Pre-Clinical Evaluations: Multiple Effects of Arachidonic Acid, its Metabolic Enzymes and Metabolites in Epilepsy.Molecular neurobiology · 2025Review
- Inhibiting the soluble epoxide hydrolase increases the EpFAs and ERK1/2 expression in the hippocampus of LiCl-pilocarpine post-status epilepticus rat model.IBRO neuroscience reports · 2024Article
- Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Novel molecular mechanism driving neuroprotection after soluble epoxide hydrolase inhibition: Insights for Alzheimer's disease therapeutics.CNS neuroscience & therapeutics · 2024Article
- Quantitative Profiling Method for Oxylipins in Neurodegenerative Diseases by Liquid Chromatography Coupled with Tandem Mass Spectrometry.bioRxiv : the preprint server for biology · 2023Article
- Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.Advances in pharmacology (San Diego, Calif.) · 2023Article
- TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model.Brain sciences · 2021Article
- Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging.JCI insight · 2021Article
- Article
- Review
- Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity.Prostaglandins, leukotrienes, and essential fatty acids · 2020Review
- Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson's Disease: A New Therapeutic Strategy.Biomolecules · 2020Review
- Cytochrome P450 derived epoxidized fatty acids as a therapeutic tool against neuroinflammatory diseases.Prostaglandins & other lipid mediators · 2020Review
- Tetramethylenedisulfotetramine neurotoxicity: What have we learned in the past 70 years?Neurobiology of disease · 2020Review
- Soluble Epoxide Hydrolase Inhibition Attenuates Excitotoxicity Involving 14,15-Epoxyeicosatrienoic Acid-Mediated Astrocytic Survival and Plasticity to Preserve Glutamate Homeostasis.Molecular neurobiology · 2019Article
- Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model.Brain, behavior, and immunity · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders.
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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.