Development of a Rat Diisopropylfluorophosphate-Induced Seizure/Status Epilepticus Model for Screening of Neuroprotectants Following Exposure to Chemical Warfare Agents

摘要

We have developed a seizure/status epilepticus (SE) rat model using diisopropylfluorophosphate (DEP), an organophosphate (OP) surrogate for chemical warfare nerve agents (CWNA) soman and sarin. Rats were surgically implanted with a radiotelemetry probe that records EEG, ECG, body temperature, and physical activity. After 1 week they were exposed to various concentrations of DFP (1.5-4.0 mg/kg, sc) in the presence of pyridostigmine bromide, 2-PAM and atropine to produce more than 24 h seizure/SE. The successful model involves administration of pyridostigmine bromide (0.026 mg/kg, im) 30 minutes prior to DEP (4.0 mg/kg) followed by a mixture of atropine (0.2 mg/kg) and 2-PAM (25 mg/kg, im). Neuropathology data in the DEP model showed maximum and more severe damage in the amygdala similar to CWNA treated animals. This animal model of seizure/SE can be used for evaluation of neuroprotectants and recombinant bioscavengers, as well as studying the molecular mechanism of neuronal death following exposure to chemical warfare agents.