ArticleToxicology and applied pharmacology2014
Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication.
Article in Toxicology and applied pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- 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
- Acute Paraoxon-Induced Neurotoxicity in a Mouse Survival Model: Oxidative Stress, Dopaminergic System Alterations and Memory Deficits.International journal of molecular sciences · 2024Article
- Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.Advances in pharmacology (San Diego, Calif.) · 2023Article
- The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats.Arquivos de neuro-psiquiatria · 2022Article
- Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus.Neurotoxicology · 2021Article
- Perampanel, a potent AMPA receptor antagonist, protects against tetramethylenedisulfotetramine-induced seizures and lethality in mice: comparison with diazepam.Archives of toxicology · 2021Article
- Review
- Susceptibility of larval zebrafish to the seizurogenic activity of GABA type A receptor antagonists.Neurotoxicology · 2020Article
- Tetramethylenedisulfotetramine neurotoxicity: What have we learned in the past 70 years?Neurobiology of disease · 2020Review
- Article
- 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
- Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation.Biochimie · 2019Review
- Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders.Progress in neurobiology · 2019Review
- Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target.Neuroscience and biobehavioral reviews · 2018Review
- Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats.Developmental neurobiology · 2018Article
- Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery.Neurotoxicology · 2017Article
- Influence of tetramethylenedisulfotetramine on synchronous calcium oscillations at distinct developmental stages of hippocampal neuronal cultures.Neurotoxicology · 2017Article
- Models to identify treatments for the acute and persistent effects of seizure-inducing chemical threat agents.Annals of the New York Academy of Sciences · 2016Review
- Tetramethylenedisulfotetramine: pest control gone awry.Annals of the New York Academy of Sciences · 2016Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABAAR) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABAAR positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15mg/kg, ip). Administration of a high dose of diazepam (5mg/kg, ip) immediately following the second clonic seizure (approximately 20min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABAAR antagonists. The sEH inhibitor TUPS (1mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5mg/kg, ip) and TUPS (1mg/kg, ip, starting 1h after diazepam and repeated every 24h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication.
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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.