Document Type
Article
Original Publication Date
2016
Journal/Book/Conference Title
Neurotoxicology and Teratology
Volume
56
First Page
81
Last Page
86
DOI of Original Publication
10.1016/j.ntt.2016.05.002
Date of Submission
October 2016
Abstract
Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival.
Rights
Copyright © 2016 Elsevier Inc. All rights reserved.
Is Part Of
VCU Neurology Publications
Included in
Neurology Commons, Neuroscience and Neurobiology Commons, Neurosciences Commons, Pharmacology, Toxicology and Environmental Health Commons
Comments
Originally published at http://doi.org/10.1016/j.ntt.2016.05.002.