Mechanisms and Treatment of OP-Induced Seizures and Neuropathology

摘要

This report summarizes studies on the mechanisms and treatment of soman-inducedseizures and neuropathology. Major goals of this work are to identify the first sites exhibiting soman-induced hyperactivity and neuropathology, and to determine if neurotransmitters other than acetylcholine (ACh) are altered by soman. Markers for c-fos and reactive astrocytes pinpointed sites of seizures and neuropathology, and neurochemistry quantified neurotransmitter levels. Piriform cortex (PC) and the noradrenergic (NE) nucleus locus coeruleus (LC) first exhibited c-fos and reactive astrocytes after soman. Seizures, c-fos and reactive astrocytes in PC were also produced by stimulation of endogenous ACh inputs to PC. Soman caused increased LC neuronal activity, producing sustained NE release leading to depletion in convulsive but not nonconvulsive rats. As NE is proconvulsant in several seizure models, we hypothesize that soman-induced NE release plays a critical role in seizure induction and/or maintenance. This work indicates that increased ACh and NE play important roles in soman-induced seizures, and suggests new therapeutic approaches involving NE antagonists. Since many NE antagonists are used clinically, their combination with ACh antagonists could provide an improved, rapidly deployed postexposure protective regimen. Soman, Acetylcholine, Acetylcholinesterase, Piriform cortex, Norepinephrine, Locus coeruleus, Seizures, Convulsions.