Age-dependent behaviors, seizure severity and neuronal damage in response to nerve agents or the organophosphate DFP in immature and adult rats
Abstract
Exposure to nerve agents (NAs) and other organophosphates (OPs) can initiate seizures that rapidly progress to status epilepticus (SE). While the electrographic and neuropathological sequelae of SE evoked by NAs and OPs have been characterized in adult rodents, they have not been adequately investigated in immature animals. In this study postnatal day (PND) 14, 21 and 28 rat pups, along with PND70 animals as adult controls, were exposed to NAs (sarin, VX) or another OP (diisopropylfluorophosphate, DFP). We then evaluated behavioral and electrographic (EEG) correlates of seizure activity, and performed neuropathology using Fluoro-Jade B. Although all immature rats exhibited behaviors that are often characterized as seizures, the incidence, duration, and severity of the electrographic seizure activity were age-dependent. No (sarin and VX) or brief (DFP) EEG seizure activity was evoked in PND14 rats, while SE progressively increased in severity as a function of age in PND21, 28 and 70 animals. Fluoro-Jade B staining was observed in multiple brain regions of animals that exhibited prolonged seizure activity. Neuronal injury in PND14 animals treated with DFP was lower than in older animals and absent in rats exposed to sarin or VX. In conclusion, we found that NAs and an OP provoked robustmore »
- Authors:
-
- Univ. of Utah, Salt Lake City, UT (United States). Department of Neurosurgery
- Aberdeen Proving Ground, MD (United States). Neuroscience Branch, U.S. Army Medical Research Institute of Chemical Defense
- Univ. of Utah, Salt Lake City, UT (United States). Department of Neurosurgery; Univ. of Utah, Salt Lake City, UT (United States). Department of Pharmacology and Toxicology
- Univ. of Utah, Salt Lake City, UT (United States). Department of Neurosurgery; Epitel, Inc., Salt Lake City, UT (United States)
- Univ. of Utah, Salt Lake City, UT (United States). Department of Pediatrics
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1623702
- Grant/Contract Number:
- SC0014664
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Neurotoxicology
- Additional Journal Information:
- Journal Volume: 66; Journal Issue: C; Journal ID: ISSN 0161-813X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
Citation Formats
Scholl, Erika A., Miller-Smith, Stephanie M., Bealer, Steven L., Lehmkuhle, Mark J., Ekstrand, Jeffrey J., Dudek, F. Edward, and McDonough, John H. Age-dependent behaviors, seizure severity and neuronal damage in response to nerve agents or the organophosphate DFP in immature and adult rats. United States: N. p., 2018.
Web. doi:10.1016/j.neuro.2018.02.018.
Scholl, Erika A., Miller-Smith, Stephanie M., Bealer, Steven L., Lehmkuhle, Mark J., Ekstrand, Jeffrey J., Dudek, F. Edward, & McDonough, John H. Age-dependent behaviors, seizure severity and neuronal damage in response to nerve agents or the organophosphate DFP in immature and adult rats. United States. https://doi.org/10.1016/j.neuro.2018.02.018
Scholl, Erika A., Miller-Smith, Stephanie M., Bealer, Steven L., Lehmkuhle, Mark J., Ekstrand, Jeffrey J., Dudek, F. Edward, and McDonough, John H. Tue .
"Age-dependent behaviors, seizure severity and neuronal damage in response to nerve agents or the organophosphate DFP in immature and adult rats". United States. https://doi.org/10.1016/j.neuro.2018.02.018. https://www.osti.gov/servlets/purl/1623702.
@article{osti_1623702,
title = {Age-dependent behaviors, seizure severity and neuronal damage in response to nerve agents or the organophosphate DFP in immature and adult rats},
author = {Scholl, Erika A. and Miller-Smith, Stephanie M. and Bealer, Steven L. and Lehmkuhle, Mark J. and Ekstrand, Jeffrey J. and Dudek, F. Edward and McDonough, John H.},
abstractNote = {Exposure to nerve agents (NAs) and other organophosphates (OPs) can initiate seizures that rapidly progress to status epilepticus (SE). While the electrographic and neuropathological sequelae of SE evoked by NAs and OPs have been characterized in adult rodents, they have not been adequately investigated in immature animals. In this study postnatal day (PND) 14, 21 and 28 rat pups, along with PND70 animals as adult controls, were exposed to NAs (sarin, VX) or another OP (diisopropylfluorophosphate, DFP). We then evaluated behavioral and electrographic (EEG) correlates of seizure activity, and performed neuropathology using Fluoro-Jade B. Although all immature rats exhibited behaviors that are often characterized as seizures, the incidence, duration, and severity of the electrographic seizure activity were age-dependent. No (sarin and VX) or brief (DFP) EEG seizure activity was evoked in PND14 rats, while SE progressively increased in severity as a function of age in PND21, 28 and 70 animals. Fluoro-Jade B staining was observed in multiple brain regions of animals that exhibited prolonged seizure activity. Neuronal injury in PND14 animals treated with DFP was lower than in older animals and absent in rats exposed to sarin or VX. In conclusion, we found that NAs and an OP provoked robust SE and neuronal injury similar to adults in PND21 and PND28, but not in PND14, rat pups. Convulsive behaviors were often present independent of EEG seizures and were unaccompanied by neuronal damage. These differential responses should be considered when investigating medical countermeasures for NA and OP exposure in pediatric populations.},
doi = {10.1016/j.neuro.2018.02.018},
journal = {Neurotoxicology},
number = C,
volume = 66,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2018},
month = {Tue May 01 00:00:00 EDT 2018}
}
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