Pediatric Susceptibility to Organophosphate-Induced Seizures and Effectiveness of Anticonvulsant Treatments
Abstract
Organophosphate (OP) poisoning can lead to seizures and even status epilepticus (SE), which is associated with high morbidity and mortality. Little data exist on OP-induced SE in immature animals, even though the immature brain is likely to respond differently to OPs, and the optimal therapies are also likely to differ from adults. Our recently published paper (Scholl, et al., 2018) details our results in designing an immature-rat model of OP-induced SE for the pediatric population using diisopropyl fluorophosphate (DFP). We found that postnatal day 21 (P21) and P28 rats developed a robust, hours-long SE in response to the OP, which was a goal of the grant. However, P7 and P14 rats had few, if any, electrographic SE events and these events were all less than 1 hr. One possible strategy to increase the duration of seizures in these very young rats would be to modify the pharmacological pretreatment that is given prior to DFP to make the brain more permissive for SE. When we replaced pyridostigmine bromide with scopolamine in P14 rats, both the occurrence of seizures and their duration was actually decreased, and mortality was increased; therefore, scopolamine was not a suitable replacement for the pyridostigmine bromide. Further experiments would be needed to further probe the utility of pharmacological adjuvants for eliciting sustained seizures. We also returned to the question of whether a P7 pup was even capable of generating and maintaining seizures. Because of our limited success using direct cholinergic (DFP) and glutamatergic (kainic acid) agonists, we tested picrotoxin, which blocks the GABAA-receptor chloride channel. Treatment of P7 pups with picrotoxin resulted in robust and frank seizure activity, which lasted up to minutes, confirming that very immature rats can have sustained seizures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2018
- Accession Number
- AD1054764
Entities
People
- Erika A. Scholl
- Francis E. Dudek
Organizations
- University of Utah