Validating a model of benzodiazepine refractory nerve agent-induced status epilepticus by evaluating the anticonvulsant and neuroprotective effects of scopolamine, memantine, and phenobarbital.

Introduction: Organophosphorus nerve agents (OPNAs) irreversibly block acetylcholinesterase activity, resulting in accumulation of excess acetylcholine at neural synapses, which can lead to a state of prolonged seizures known as status epilepticus (SE). Benzodiazepines, the current standard of care for SE, become less effective as latency to treatment increases. In a mass civilian OPNA exposure, concurrent trauma and limited resources would likely cause a delay in first response time.

Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure.

Exposure to nerve agents results in severe seizures or status epilepticus caused by the inhibition of acetylcholinesterase, a critical enzyme that breaks down acetylcholine to terminate neurotransmission. Prolonged seizures cause brain damage and can lead to long-term consequences. Current countermeasures are only modestly effective against the brain damage supporting interest in the evaluation of new and efficacious therapies.