Age-Dependent Behaviors, Seizure Severity and Neuronal Damage in Response to Nerve Agents or the Organophosphate DFP in Immature and Adult Rats
Journal Article - Open Access
U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground
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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 neuronalinjury 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.
- Chemical, Biological and Radiological Warfare