Seizure Susceptibility and Developmental Alterations of Pediatric Rats After OP Status Epilepticus: Mitigation by Novel Anticonvulsants
Abstract number :
3.282
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2022
Submission ID :
2204990
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Tanveer Singh, PhD – Texas A & m university; Sreevidhya Ramakrishnan, PhD – Neuroscience and Experimental Therapeutics; Xin Wu, MD – Assistant Professor, Neuroscience and experimental therapeutics, Texas A & m university; D. Samba Reddy, PhD – Texas A & m university
Rationale: Children are more susceptible to the neurotoxic effects of organophosphates (OP) and nerve agents. Children are at risk for exposure to OP pesticides and developmental neurotoxic risk is of critical concern. Pediatric OP exposure can lead to vulnerability to seizures and behavior dysfunction. However, there are very few pediatric OP models to simulate features of children’s exposure to OP agents. In this study, we investigated the developmental impact of neonatal exposure to the OP compound diisopropylfluorophosphate (DFP) on cognitive and behavioral patterns in pediatric rats.
Methods: Pediatric P21 rat pups were exposed to DFP-induced status epilepticus (SE) and were treated with a novel neurosteroid (NS) analog along with standard antidote regimens. They were assessed for behavior deficits for next 3 months. Seizures were monitored by 24/7 video-EEG recording and analyzed for both ictal and interictal activity.
Results: Animals exposed to DFP at P21 age exhibited significant behavioral deficits, including mood and memory impairments. They displayed aggressive behavior, heightened anxiety, depressive response, and memory deficits. The DFP-exposed rats exhibited persistent hyperexcitability with an increase in seizures, discharges, HFOs, and interictal spikes. Seizure frequency and behavior deficits were significantly lower in the NS drug-treated cohort.
Conclusions: These results confirm greater seizure susceptibility and behavioral deficits after neonatal OP exposure, suggesting the validity of this pediatric model for therapeutic interventions.
Funding: This work was supported by NIH Grant #U01-NS117209 (to D.S.R.).
Anti-seizure Medications