Magnetic resonance imaging reveals that galantamine prevents structural brain damage induced by an acute exposure of guinea pigs to soman
Magnetic resonance imaging reveals that galantamine prevents structural brain damage induced by an acute exposure of guinea pigs to soman
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DOI：
10.1016/j.neuro.2009.09.004
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发表时间：
2010-01-01
期刊：
影响因子：
3.4
通讯作者：
Albuquerque, Edson X.
中科院分区：
文献类型：
--
作者：
Gullapalli, Rao P.;Aracava, Yasco;Albuquerque, Edson X.
加兰他敏是一种用于治疗阿尔茨海默病的药物，最近已成为对抗有机磷（OP）化合物（包括神经毒剂梭曼）毒性的潜在医疗对策。在这里，磁共振成像（MRI）用于表征梭曼的神经毒性作用和加兰他敏在豚鼠中预防这些作用的能力，豚鼠是预测人类OP毒性解毒剂有效性的最佳非灵长类动物模型。在用1.0xLD 50梭曼（26.6 μ g/kg，sc）攻击前48小时和攻击后6-7小时、48小时和7天，使用临床3.0特斯拉MRI扫描仪对处理和未处理的豚鼠的脑进行成像。在用梭曼攻击后7天，在所有未处理的动物中观察到显著的脑萎缩。在轻度中毒的动物，显着缩短自旋-自旋弛豫时间（T2）观察到丘脑和杏仁核在7小时后的挑战。在严重中毒的动物，T2值和T2加权信号强度显着增加，梨状皮质，海马，丘脑和杏仁核：在大多数地区，变化是持久的。基于体素的图像形态学分析显示，这些动物的其他大脑区域也受到了损害。病理组织学证实神经元丢失。在暴露于梭曼前30分钟用加兰他敏（8 mg/kg，im）处理的动物中，T2、T2加权信号强度和CSF体积基本上不受影响。结论：加兰他敏能有效预防急性梭曼暴露所致的脑结构损伤。(C)2009年由Elsevier Inc.出版
Galantamine, a drug used to treat Alzheimer's disease, has recently emerged as a potential medical countermeasure against the toxicity of organophosphorus (OP) compounds, including the nerve agent soman. Here, magnetic resonance imaging (MRI) was used to characterize the neurotoxic effects of soman and the ability of galantamine to prevent these effects in guinea pigs, the best non-primate model to predict the effectiveness of antidotes against OP toxicity in humans. The brains of treated and untreated guinea pigs were imaged using a clinical 3.0 Tesla MRI scanner at 48 h before and 6-7 h, 48 h and 7 days after their challenge with 1.0xLD50 soman (26.6 mu g/kg, sc). Significant brain atrophy was observed among all untreated animals at 7 days after their challenge with soman. In mildly intoxicated animals, significant shortening of spin-spin relaxation times (T2) was observed in the thalamus and amygdala at 7 h after the challenge. In severely intoxicated animals, T2 values and T2-weighted signal intensities increased significantly in the piriform cortex, hippocampus, thalamus and amygdala: in most regions, changes were long-lasting. Voxel-based morphometric analysis of the images revealed that other brain regions were also damaged in these animals. Neuronal loss was confirmed histopathologically. In animals that were treated with galantamine (8 mg/kg, im) 30 min prior to the exposure to soman, T2, T2-weighted signal intensities, and CSF volumes were largely unaffected. It is, therefore, concluded that galantamine can effectively prevent the structural brain damage induced by an acute exposure to soman. (C) 2009 Published by Elsevier Inc.