ArticleEuropean journal of pharmacology2020
Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.
Article in European journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Neurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation.Frontiers in toxicology · 2026Article
- Article
- Organophosphate Chemical Nerve Agents, Oxidative Stress, and NADPH Oxidase Inhibitors: An Overview.International journal of molecular sciences · 2025Review
- The key role of magnesium sulfate in the management of organophosphorus pesticide poisoning: a scoping literature review.Clinical and experimental emergency medicine · 2025Article
- Article
- 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
- A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures.Neuropharmacology · 2024Article
- Quantitative TNeuropharmacology · 2024Article
- Fully automated whole brain segmentation from rat MRI scans with a convolutional neural network.Journal of neuroscience methods · 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
- 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
- Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.Frontiers in toxicology · 2024Article
- The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity.Antioxidants (Basel, Switzerland) · 2023Article
- Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus.Neurobiology of disease · 2023Article
- Peripheral and central effects of NADPH oxidase inhibitor, mitoapocynin, in a rat model of diisopropylfluorophosphate (DFP) toxicity.Frontiers in cellular neuroscience · 2023Article
- Cognitive Impairment and Neurodegenerative Diseases Development Associated with Organophosphate Pesticides Exposure: a Review Study.Neurotoxicity research · 2022Review
- Microglia Remodelling and Neuroinflammation Parallel Neuronal Hyperactivation Following Acute Organophosphate Poisoning.International journal of molecular sciences · 2022Article
- Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus.Neurotoxicology · 2021Article
- Mechanisms of organophosphate neurotoxicity.Current opinion in toxicology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
Acute intoxication with organophosphorus cholinesterase inhibitors (OPs) can trigger seizures that rapidly progress to life-threatening status epilepticus. Diazepam, long considered the standard of care for treating OP-induced seizures, is being replaced by midazolam. Whether midazolam is more effective than diazepam in mitigating the persistent effects of acute OP intoxication has not been rigorously evaluated. We compared the efficacy of diazepam vs. midazolam in preventing persistent neuropathology in adult male Sprague-Dawley rats acutely intoxicated with the OP diisopropylfluorophosphate (DFP). Subjects were administered pyridostigmine bromide (0.1 mg/kg, i.p.) 30 min prior to injection with DFP (4 mg/kg, s.c.) or vehicle (saline) followed 1 min later by atropine sulfate (2 mg/kg, i.m.) and pralidoxime (25 mg/kg, i.m.), and 40 min later by diazepam (5 mg/kg, i.p.), midazolam (0.73 mg/kg, i.m.), or vehicle. At 3 and 6 months post-exposure, neurodegeneration, reactive astrogliosis, microglial activation, and oxidative stress were assessed in multiple brain regions using quantitative immunohistochemistry. Brain mineralization was evaluated by in vivo micro-computed tomography (micro-CT). Acute DFP intoxication caused persistent neurodegeneration, neuroinflammation, and brain mineralization. Midazolam transiently mitigated neurodegeneration, and both benzodiazepines partially protected against reactive astrogliosis in a brain region-specific manner. Neither benzodiazepine attenuated microglial activation or brain mineralization. These findings indicate that neither benzodiazepine effectively protects against persistent neuropathological changes, and suggest that midazolam is not significantly better than diazepam. Overall, this study highlights the need for improved neuroprotective strategies for treating humans in the event of a chemical emergency involving OPs.
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