Abstracts

This is a Late Breaking abstract

Rationale: Children are more susceptible to seizures and the neurotoxic effects of organophosphates (OP) and nerve agents. Both children and neonates are at risk for exposure to OP pesticides, with whom developmental risks are a critical concern. Pediatric OP exposure can lead to acute seizures and neuropsychiatric sequela including developmental disabilities and cognitive impairments. However, there are few epilepsy models that use pediatric OP exposure for studying neuron developmental consequences and interventions.

Methods: In this study, we investigated the long-term developmental impact of neonatal exposure to the OP compound diisopropyl fluorophosphate (DFP) that induced status epilepticus (SE) in pediatric rats. P28 rat pups were exposed to DFP and were treated with midazolam and an atropine regimen for seizure control and survival. Ten months after exposure, animals were evaluated in an array of mood and behavior tests such as open-field, plus-maze, novel object recognition, and water-maze memory testing.

Results: At 10 months post-SE, animals displayed significant deficits in mood and anxiety behavior compared to age-matched controls. Animals displayed marked aggressive traits, deficits in object recognition memory, and decreased ability in spatial learning and memory. Neurosteroid treatment resulted in an improved index of mood and cognition as compared to the control group.

Conclusions: This pediatric model replicates many features of children with OP-SE. This suggests its viability for therapeutic screenings, such as testing neuroprotectant interventions.

Funding: This work was supported by NIH Grant U01-NS117209.