Imidazenil: A Protective Agent Against Chemical Warfare Agents induced Status Epilepticus

The overall objective of this proposal is to demonstrated that imidazenil is a more potent and safer protective agent than diazepam against chemical warfare nerve agent (CWNA)-induced seizure/status epilepticus, neuropathology, and neurobehavioral deficits. Thus we will compare the dose-dependent efficacy of imidazenil or diazepam administered alone and in combination with levetiracetam in protecting rats against diisopropyl fluorophosphate (DFP)-induced toxicity using the following 2 aims. Aim I: To evaluate the dose-dependent efficacies of imidazenil or diazepam administered alone or in combination with levetiracetam in the absence or presence of atropine and/or pralidoxime chloride (2-PAM) against DFP-induced seizure/status epilepticus and neurobehavioral deficits. This will be achieved by telemetric monitoring of cortical electroencephalogram (EEG), core temperature and motor activity. Aim II: To evaluate the effects of imidazenil or diazepam administered alone or in combination with levetiracetam in the absence or presence of atropine and/or 2-PAM on DFP-induced neuropathology. Rat brains will be examined for neuronal degeneration using the deoxyribonucleic acid (DNA) fragmentation measurement and light microscopy histological analysis. These studies may provide new information regarding the potential role of imidazenil in the treatment or prevention of CWNA poisoning and the potential role of the combination of levetiracetam and imidazenil in minimizing CWNA-induced neuropathology.