In vivo microdialysis and EEG recording have been used in order to study the combined neurochemical and electrophysiological events during intoxication with soman (o-1,2,2-trimethylpropyl methylphosphono-fluoridate), a potent inhibitor of acetylcholinesterase (AChE), in the freely moving rat. All rats exposed to soman exhibited signs of AChE inhibition. The duration of EEG recorded seizures after soman intoxication averaged 43 +/- 24 min. The extracellular striatal levels of dopamine and GABA, increased significantly during the EEG seizure periods. Using an EEG based differentiation between seizure and non-seizure conditions, we found that intrastriatal release of dopamine, but not glutamate, during soman intoxication is highly correlated with seizures. Our results suggest that excitatory amino acids (EAA) involvement in soman-induced seizures, as demonstrated in hippocampus, may not be relevant in the striatum. Our data, instead, may indicate the importance of dopamine as a neurotoxic agent.
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http://dx.doi.org/10.1016/s0304-3940(97)00552-1 | DOI Listing |
Toxicol Lett
November 2024
Bundeswehr Institute for Pharmacology and Toxicology, Neuherbergstraße 11, Munich 80937, Germany. Electronic address:
Neurotox Res
September 2024
Neuroscience Department, Medical Toxicology Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, 21010-5400, USA.
Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A adenosine receptor (AAR) agonist N-bicyclo-(2.2.
View Article and Find Full Text PDFNeuropharmacology
August 2024
Medical Toxicology Research Division, U.S. Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010-5400, USA. Electronic address:
Exposure to organophosphorus compounds, such as soman (GD), cause widespread toxic effects, sustained status epilepticus, neuropathology, and death. The A adenosine receptor agonist N-bicyclo-(2.2.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
January 2024
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa (M.P., S.S.V., N.S.R., C.M., M.V.O., L.T., T.T.); Department of Radiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa (D.R.T.); and Department of Radiology, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, New Jersey (S.S.K.)
Organophosphate (OP) nerve agent (OPNA) intoxication leads to long-term brain dysfunctions. The ineffectiveness of current treatments for OPNA intoxication prompts a quest for the investigation of the mechanism and an alternative effective therapeutic approach. Our previous studies on 1400W, a highly selective inducible nitric oxide synthase (iNOS) inhibitor, showed improvement in epilepsy and seizure-induced brain pathology in rat models of kainate and OP intoxication.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
January 2024
Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado (L.-P.L., J.N.P.-S., B.J.D., M.P.); and Department of Medicine, National Jewish Health, Denver, Colorado (B.J.D.)
Reactive oxygen species have an emerging role in the pathologic consequences of status epilepticus. We have previously demonstrated the efficacy of a water-for-injection formulation of the -porphyrin catalytic antioxidant, manganese (III) -tetrakis (--diethylimidazole) porphyrin (AEOL10150) against oxidative stress, neuroinflammation, and neuronal death initiated by kainic acid, pilocarpine, diisopropylflurophosphate (DFP), and soman. This previous dose and dosing strategy of AEOL10150 required smaller multiple daily injections, precluding our ability to test its efficacy against delayed consequences of nerve agent exposure such as neurodegeneration and cognitive dysfunction.
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