ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Editor's Highlight: Spatiotemporal Progression and Remission of Lesions in the Rat Brain Following Acute Intoxication With Diisopropylfluorophosphate.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. 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, 54 citations in OpenAlex.
- Article
- Spatiotemporal perturbations of the plasminogen activation system in a rat model of acute organophosphate intoxication.Acta neuropathologica communications · 2025Article
- Allopregnanolone as an Adjunct Therapy to Midazolam is More Effective Than Midazolam Alone in Suppressing Soman-Induced Status Epilepticus in Male Rats.CNS neuroscience & therapeutics · 2025Article
- 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
- Quantitative TNeuropharmacology · 2024Article
- Fully automated whole brain segmentation from rat MRI scans with a convolutional neural network.Journal of neuroscience methods · 2024Article
- Novel Catalytic Antioxidant Formulation Decreases Oxidative Stress, Neuroinflammation and Cognitive Dysfunction in a Model of Nerve Agent Intoxication.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
- Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.The Journal of pharmacology and experimental therapeutics · 2024Review
- Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.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
- Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus.Neurobiology of disease · 2023Article
- The Association between Pesticide Exposure and the Development of Fronto-Temporal Dementia-Cum-Dissociative Disorders: A Review.Brain sciences · 2023Review
- Novel image analysis tool for rapid screening of cell morphology in preclinical animal models of disease.Heliyon · 2023Article
- 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
- Persistent neuropathology and behavioral deficits in a mouse model of status epilepticus induced by acute intoxication with diisopropylfluorophosphate.Neurotoxicology · 2021Article
- Comparative profile of refractory status epilepticus models following exposure of cholinergic agents pilocarpine, DFP, and soman.Neuropharmacology · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading to convulsions that can progress to status epilepticus (SE). However, in contrast to the OP nerve agents, the long-term consequences of DFP-induced SE are not well known. Thus, we characterized the spatiotemporal profile of neuropathology during the first 2 months following acute DFP intoxication. Adult, male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im), exhibited moderate-to-severe seizure behavior, yet survived until euthanized at 0.5 to 60 days post exposure. Analyses of brains and hearts stained with hematoxylin-eosin, or of brains immunostained for neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), or ionized binding adapter molecule 1 (IBA1), revealed progressive neuronal cell death, neuroinflammation, and tissue remodeling across limbic brain regions and the cerebral cortex, with no detectable pathology in the cerebellum or the heart. The lesion type and progression varied according to brain region and time after exposure. Across multiple brain regions, neuronal necrosis peaked after the first week, and neuroinflammation persisted at least 2 months after intoxication. Notably, mineralization was observed at later times in the thalamus, and to a more limited extent, in the hippocampus. Lesion severity was influenced by the initial seizure severity, and spontaneous recurrent seizures were associated with more severe brain damage. These findings parallel descriptions of neuropathology in preclinical models of acute intoxication with OP nerve agents, and other seizurogenic chemicals, suggesting conserved mechanisms of pathology downstream of chemical-induced SE.
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