title: Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy.
abstract: Epilepsy is a common neurological disorder characterized by an initial injury due to stroke, traumatic brain injury, brain infection, or febrile seizures causing status epilepticus (SE). This phenomenon precedes recurrent (secondary) seizures, the latent period (period without seizures) and downstream appearance of spontaneous recurrent seizures (SRS). Epilepsy inducers include the organophosphorous (OP) compounds modified as chemical warfare nerve agents, such as soman. SE induced by soman is a result of cholinergic system hyperactivity caused by the irreversible inhibition of acetylcholinesterase, and the subsequent increase in the amount of the neurotransmitter acetylcholine at central and peripheral sites. SE leads to profound, permanent, complex and widespread brain damage and associated cognitive and behavioral deficits, accompanied by impaired neurogenesis. Several anticonvulsant and neuroprotective strategies have been studied in order to avoid the epileptogenesis which occurs after SE caused by soman exposure. In recent studies, we showed that SRS occur post-soman exposure and neuropathology can be reduced with diazepam (DZP) and valproic acid (VPA) when administered in combination treatment. These effects are accompanied by neurogenesis seen 15 days post-exposure in the hippocampal dentate gyrus (DG). This review discusses several findings about epilepsy induced by soman exposure such as behavioral changes, EEG anomalies, neuropathology, neuroinflammation, neurogenesis, possible circuitry changes and current strategies for treatment. The soman seizure model is an important model of temporal lobe epilepsy (TLE) and comparable in certain respects with well studied models in the literature such as pilocarpine and kainic acid. All these models together allow for a greater understanding of the different mechanisms of seizure induction, propagation and options for treatment. These studies are very necessary for current military and civilian treatment regimens, against OP nerve agent exposure, which fail to prevent SE resulting in severe neuropathology and epilepsy.
authors.affiliation: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
authors.forename: Marcio
authors.initials: M
authors.lastname: de Araujo Furtado
authors.affiliation: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
authors.forename: Franco
authors.initials: F
authors.lastname: Rossetti
authors.affiliation: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
authors.forename: Soma
authors.initials: S
authors.lastname: Chanda
authors.affiliation: Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States. Electronic address: debra.yourick@us.army.mil.
authors.forename: Debra
authors.initials: D
authors.lastname: Yourick
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000931:Antidotes / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D058256:Brain Waves / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004660:Encephalitis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012999:Soman / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012999:Soman