1 Protection against Chemical Agent - Induced , Seizure - Related Neuronal Cell Death

Organophosphorus nerve agents are the most toxic chemical warfare agents that present a threat to the warfighter. Irreversible inhibition of acetylcholinesterase, by nerve agents leads to accumulation of the neurotransmitter acetylcholine (ACh) at cholinergic synapses (Taylor, 1996). Currently fielded MARK I nerve agent antidote for treatment of nerve agent poisoning protects against life threatening consequences (Dunn and Sidell 1989). When (ACh) accumulates in excess amounts it can initiate seizure activity. Soldiers surviving the initial life threatening effects of nerve agent poisoning are likely to develop seizure activity. Seizures perturb other neurotransmitter systems and release the excitatory animo acid (EAA) glutamate. The EAA then assumes control of the seizures and progression to status epilepticus (SE) (McDonough and Shih, 1993) . Sustained release of glutamate and excessive stimulation of EAA receptors triggers delayed secondary excitotoxic biochemical changes involving a complex cascade of factors such as intracellular calcium overload, lipid peroxidation and free radical development, all of which contribute to neuronal cell death (Olney et al., 1983).