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

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Molecular and Chemical Neuropathology

Abstract

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 μg/kg, i.e., 1.25 × 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). GM1-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 GM1-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 somanchallenged rats that were not infused with GM1. 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 GM1 pretreatment interferes with the development of SE and significantly alleviates brain damage resulting from soman-induced seizures.

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Authors and Affiliations

  1. Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, 21010, Aberdeen Proving Ground, MD

    Frank J. Cann, Catherine D. Smith, Jeffry S. Forster, Cathleen E. Kling & Margaret G. Filbert

  2. Department of Biology, La Salle University, 19141, Philadelphia, PA

    Gerald P. H. Ballough

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  1. Gerald P. H. Ballough
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  2. Frank J. Cann
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  3. Catherine D. Smith
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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as the views of the Department of the Army. In conducting the research described in this article, the investigators adhered to the “Guide for the Care and Use of Laboratory Animals” as adopted and promulgated by the National Institutes of Health publication 96-01.

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Ballough, G.P.H., Cann, F.J., Smith, C.D. et al. GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage. Molecular and Chemical Neuropathology 34, 1–23 (1998). https://doi.org/10.1007/BF02815133

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