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The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE).

The effect of intravenous mannitol on soman-induced neuropathology and cardiomyopathy was studied in rats. Soman, an organophosphorus agent, irreversibly inhibits total body acetylcholinesterase and induces a cholinotoxic syndrome in rats which results in the development of seizures, brain damage, and degenerative cardiomyopathy. The severity of the cardiomyopathy parallels the severity of the neuropathology. When mannitol at a dose of 1.5 g/kg was administered at the onset of seizures and followed by a second dose 5 h later, there was a significant increase in 24 h survival. Moreover, the severity of brain lesions was reduced in the piriform cortex, thalamus, amygdala, and the caudate putamen. The same treatment schedule also provided almost complete protection against the concomitant development of degenerative cardiomyopathy. The finding that the mannitol treatments reduced both the severity o f the neuropathology and the degenerative cardiomyopathy reinforces the concept of a possible central neurogenic mechanism for the development of the cardiomyopathy. These results suggest that mannitol may be useful t o reduce the severity of seizure-related neuropathology and to provide additional protection to other vital organs which may be secondarily susceptible t o neurogenically mediated pathologic change, such as the heart in rats which develop cardiomyopathy following soman-induced seizures.0 1993 Wiley-Liss, Inc.*

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