GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage

The effects of GM(1) monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM(1) via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 mu g/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 GM(1) (n = 14) developed status epilepticus (SE). GM(1)-infused, soman-challenged rats (n = 11) showed initial signs of seizures; however, only five developed SE. The remaining six recovered and had no brain damage. In addition, the latter group showed a significantly higher residual AChE reactivity in the basolateral amygdala compared to rats that developed SE. Quantitative image analysis of MAP2-immunostained brain sections from the five GM(1)-infused rats that developed SE showed a 85.9 +/- 14.1% reduction in cross-sectional area of necrosis in the piriform cortex when compared to the soman-challenged rats that were not infused with GM(1). This was paralleled by a pronounced decrease in morphological evidence of damage on H&E and CV-stained serial sections. Considerable brain region/treatment group variability was seen with GFAP immunostaining. The present findings demonstrate that GM(1) pretreatment interferes with the development of SE and significantly alleviates brain damage resulting from soman-induced seizures.