Mapping of Cortical Metabolic Activation in Soman-Induced Convulsions in Rats

Abstract

The metabolic activation of the cerebral cortex during convulsions induced by the organophosphorus cholinesterase inhibitor soman was studied in detail. Soman was given at a dose equivalent to 0.9 LD50 (100 μg/kg SC after pretreatment with 26 μg/kg pyridostigmine, IM, to decrease lethality) to examine separately the metabolic effects of severe acetylcholinesterase inhibition, present always with this dose, and convulsions, present only in some of the animals. Cerebral glucose utilization (CGU) values of cortex divided by CGU of brain stem (nCGU) were calculated for 96 locations in nine coronal slices. Animals injected with pyridostigmine-soman and that developed convulsions (n = 7) showed statistically significant increases of nCGU with regard to animals injected with saline (n = 5) in 33 locations, 27 of which were in a single cluster, with the piriform cortex at its center. Perirhinal cortex, and insular cortex also showed significantly higher nCGU in convulsing rats. Other foci of elevated nCGU were found in frontal and parietal locations. In animals injected with pyridostigmine-soman and that did not develop convulsions (n = 5) in spite of severe cholinesterase inhibition, a single location (piriform cortex) showed significantly higher nCGU than controls. Neuropathology evaluation showed a significant decrease in viable cells only in animals that developed convulsions. This effect correlated with enhanced nCGU. It is concluded that the presence of convulsions, and not exposure to pyridostigmine-soman, determined the pattern of nCGU cortical activation, which correlated closely with the structural changes.