ArticleBiochimica et biophysica acta. Molecular basis of disease2018
Benzodiazepine-refractory status epilepticus, neuroinflammation, and interneuron neurodegeneration after acute organophosphate intoxication.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Intentional Large-Volume Diazinon Ingestion Complicated by Seizure and Acute Respiratory Failure: A Case Report.Cureus · 2026Article
- Spatiotemporal perturbations of the plasminogen activation system in a rat model of acute organophosphate intoxication.Acta neuropathologica communications · 2025Article
- A Comprehensive Stereology Method for Quantitative Evaluation of Neuronal Injury, Neurodegeneration, and Neurogenesis in Brain Disorders.Current protocols · 2024Article
- Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate.Journal of neuroinflammation · 2024Article
- scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate.International journal of molecular sciences · 2024Article
- A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures.Neuropharmacology · 2024Article
- Tiger nut/coconut dietary intervention as antidotal nutritional remediation strategy against neurobehavioural deficits following organophosphate-induced gut-brain axis dysregulation in mice.Toxicology reports · 2024Article
- Quantitative TNeuropharmacology · 2024Article
- Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.The Journal of pharmacology and experimental therapeutics · 2024Article
- Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.The Journal of pharmacology and experimental therapeutics · 2024Article
- Protective Activity of Novel Hydrophilic Synthetic Neurosteroids on Organophosphate Status Epilepticus-induced Chronic Epileptic Seizures, Non-Convulsive Discharges, High-Frequency Oscillations, and Electrographic Ictal Biomarkers.The Journal of pharmacology and experimental therapeutics · 2024Article
- Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic.The Journal of pharmacology and experimental therapeutics · 2024Review
- A Pediatric Rat Model of Organophosphate-Induced Refractory Status Epilepticus: Characterization of Long-Term Epileptic Seizure Activity, Neurologic Dysfunction and Neurodegeneration.The Journal of pharmacology and experimental therapeutics · 2024Article
- Long-Term Neuropsychiatric Developmental Defects after Neonatal Organophosphate Exposure: Mitigation by Synthetic Neurosteroids.The Journal of pharmacology and experimental therapeutics · 2024Article
- Brief isoflurane administration as an adjunct treatment to control organophosphate-induced convulsions and neuropathology.Frontiers in pharmacology · 2023Article
- Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and Therapeutic Interventions for Acute and Chronic Neurological Disorders.International journal of molecular sciences · 2022Review
- Microglia Remodelling and Neuroinflammation Parallel Neuronal Hyperactivation Following Acute Organophosphate Poisoning.International journal of molecular sciences · 2022Article
- A review of chemical warfare agents linked to respiratory and neurological effects experienced in Gulf War Illness.Inhalation toxicology · 2022Review
- Saracatinib, a Src Tyrosine Kinase Inhibitor, as a Disease Modifier in the Rat DFP Model: Sex Differences, Neurobehavior, Gliosis, Neurodegeneration, and Nitro-Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nerve agents and some pesticides such as diisopropylfluorophosphate (DFP) cause neurotoxic manifestations that include seizures and status epilepticus (SE), which are potentially lethal and carry long-term neurological morbidity. Current antidotes for organophosphate (OP) intoxication include atropine, 2-PAM and diazepam (a benzodiazepine for treating seizures and SE). There is some evidence for partial or complete loss of diazepam anticonvulsant efficacy when given 30 min or later after exposure to an OP; this condition is known as refractory SE. Effective therapies for OP-induced SE are lacking and it is unclear why current therapies do not work. In this study, we investigated the time-dependent efficacy of diazepam in the nerve agent surrogate DFP model of OP intoxication on seizure suppression and neuroprotection in rats, following an early and late therapy. Diazepam (5 mg/kg, IM) controlled seizures when given 10 min after DFP exposure ("early"), but it was completely ineffective at 60 or 120 min ("late") after DFP. DFP-induced neuronal injury, neuroinflammation, and neurodegeneration of principal cells and GABAergic interneurons were significantly reduced by early but not late therapy. These findings demonstrate that diazepam failed to control seizures, SE and neuronal injury when given 60 min or later after DFP exposure, confirming the benzodiazepine-refractory SE and brain damage after OP intoxication. In addition, this study indicates that degeneration of inhibitory interneurons and inflammatory glial activation are potential mechanisms underlying these morbid outcomes of OP intoxication. Therefore, novel anticonvulsant and neuroprotectant antidotes, superior to benzodiazepines, are desperately needed for controlling nerve agent-induced SE and brain injury.
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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.