GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage
GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage
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DOI：
10.1007/bf02815133
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Filbert, MG
中科院分区：
文献类型：
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作者：
Ballough, GPH;Cann, FJ;Filbert, MG
本研究观察了GM(1)单唾液酸神经节苷脂预处理对梭曼致痫所致脑损伤的影响。雄性SD大鼠脑室内注入GM(1)，4d后给予梭曼(83µg/kg，1.25×LD50)刺激。通过留置皮质电极监测皮层脑电记录。给药后27h，麻醉大鼠经心内灌流缓冲多聚甲醛处死。苏木精-伊红(H&E)、甲酚紫(CV)和乙酰胆碱酯酶(AChE)组织化学染色，胶质纤维酸性蛋白(GFAP)和微管相关蛋白2(MAP2)免疫组织化学染色。所有未注射GM(1)的梭曼攻击大鼠(n=14)均出现癫痫持续状态(SE)。注射GM(1)、梭曼激发的大鼠(n=11)表现出癫痫的初步迹象；然而，只有5只发展为SE。剩下的六人康复了，没有脑损伤。此外，与发生SE的大鼠相比，后一组大鼠杏仁基底外侧核内残留的AChE反应性显著升高。定量图像分析显示，与未注射GM(1)的梭曼组大鼠相比，注射GM(1)的5只患SE的大鼠梨状皮质坏死横截面积减少了85.9+/-14.1%。与此相平行的是，在HE和CV染色的连续切片上，损伤的形态证据明显减少。GFAP免疫组织化学染色显示脑区域/治疗组有相当大的变异。本研究结果表明，GM(1)可干扰SE的发育，显著减轻梭曼致痫所致的脑损伤。
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.