Journal article
Evaluation of fosphenytoin, levetiracetam, and propofol as treatments for nerve agent-induced seizures in pediatric and adult rats
Neurotoxicology (Park Forest South), v 79(C), pp 58-66
01 Jul 2020
PMID: 32220603
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
•Male and female immature and adult rats were exposed to the nerve agents sarin or VX to elicit status epilepticus (SE) seizures.•The animals were treated with doses of fosphenytoin, levetiracetam or propofol, three drugs commonly used as second line treatment of SE.•Only propofol was very effective in terminating nerve agent-induced SE in all age groups and sexes.•Fosphenytoin and levetiracetam showed no evidence of modifying the seizures or protecting against seizure-induced neuropathology.•Propofol should be considered a treatment of choice for nerve agent-induced SE refractory to first line anticonvulsant treatment.
Multiple recent instances of nerve agent (NA) exposure in civilian populations have occurred, resulting in a variety of negative effects and lethality in both adult and pediatric populations. Seizures are a prominent effect of NAs that can result in neurological damage and contribute to their lethality. Current anticonvulsant treatments for NAs are approved for adults, but no approved pediatric treatments exist. Further, the vast majority of NA-related research in animals has been conducted in adult male subjects. There is a need for research that includes female and pediatric populations in testing. In this project, adult and pediatric male and female rats were challenged with sarin or VX and then treated with fosphenytoin, levetiracetam, or propofol. In this study, fosphenytoin and levetiracetam failed to terminate seizure activity when animals were treated 5 min after seizure onset. Propofol was effective, exhibiting high efficacy and potency for terminating seizure activity quickly in pediatric and adult animals, suggesting it may be an effective anticonvulsant for NA-induced seizures in pediatric populations.
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Details
- Title
- Evaluation of fosphenytoin, levetiracetam, and propofol as treatments for nerve agent-induced seizures in pediatric and adult rats
- Creators
- Emily N. Dunn - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USALiana M. Matson - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAKari M. Haines - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAKimberly A. Whitten - DEVCOM Army Research LaboratoryRobyn B. Lee-Stubbs - Office of the Commander, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAKyle E. Berger - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAHilary S. McCarren - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USACherish E. Ardinger - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USACecelia E. Jackson Piercy - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAStephanie M. Miller-Smith - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USAJohn H. McDonough - Neuroscience Branch, US Army Medical Research Institute of Chemical Defense, 8350 Ricketts Point Road, Aberdeen Proving Ground, MD, 21010, USA
- Publication Details
- Neurotoxicology (Park Forest South), v 79(C), pp 58-66
- Publisher
- Elsevier B.V
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000549312800007
- Scopus ID
- 2-s2.0-85083831157
- Other Identifier
- 991022054302104721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Toxicology