DIRECT MICROINJECTION OF SOMAN OR VX INTO THE AMYGDALA PRODUCES REPETITIVE LIMBIC CONVULSIONS AND NEUROPATHOLOGY
DIRECT MICROINJECTION OF SOMAN OR VX INTO THE AMYGDALA PRODUCES REPETITIVE LIMBIC CONVULSIONS AND NEUROPATHOLOGY
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DOI：
10.1016/0006-8993(87)91593-9
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发表时间：
1987-12-01
期刊：
影响因子：
2.9
通讯作者：
NIPWODA, MT
中科院分区：
文献类型：
--
作者：
MCDONOUGH, JH;MCLEOD, CG;NIPWODA, MT
在大鼠的杏仁核和其他前脑部位注射了摩尔数量的剧毒有机磷“神经毒剂”化合物梭曼或VX(O-ethyl-S-(2-diisopropylaminoethyl)-methylphosphonothioate)，以试图确定导致全身中毒后观察到的永久性脑病理的机制(S)。在氟烷/氧气麻醉下维持的动物中，使用立体定向引导的微型注射器进行注射，或者在清醒动物中使用长期植入的套管进行注射。双侧微量注射器向杏仁核注射高达11.0nmol的梭曼未能引起异常行为或脑病理。当用氯化锂预处理大鼠，或同时注射卡巴胆碱时，梭曼注射会引起反复的阵挛抽搐和神经病理。单侧杏仁核注射3.4nmolVX可引起67%的受试者抽搐和脑损伤。阿托品预处理(15.0 mg/kg，i.p.)防止痉挛和脑损伤的发展。只有反复抽搐的动物才能观察到神经病理学：梨状皮质和内嗅觉皮质、杏仁核、海马体和丘脑是受损最严重的大脑结构。在单侧注射的情况下，注射侧的损伤更为严重。抽搐的行为地形图以及随后病理的神经解剖分布和性质与全身应用这些化合物所观察到的非常相似。结果表明，这些神经毒剂没有直接的神经毒性，外周诱导的缺氧或缺氧不太可能是神经病理的机制，这些化合物造成的脑损伤主要是由癫痫介导的。
Rats were injected in the amygdala and other forebrain sites with nmolar amounts of the highly toxic organophosphate ''nerve agent'' compounds soman or VX (O-ethyl-S-(2-diisopropylaminoethyl)-methylphosphonothioate) in an attempt to determine the mechanism(s) responsible for the permanent brain pathology that has been observed following systemic intoxication with these agents. Injections were performed using a stereotaxically guided microsyringe in animals maintained under halothane/oxygen anesthesia or using chronically implanted cannulae in conscious animals. Bilateral microsyringe injections of up to 11.0 nmol soman into the amygdala failed to evoke abnormal behavior or brain pathology. When rats were pretreated with lithium chloride, or when carbachol was coadministered, soman injections evoked repetitive clonic convulsions and neuropathology. Unilateral injections of 3.4 nmol of VX into the amygdala elicited convulsions and brain damage in 67% of the animals tested. Atropine pretreatment (15.0 mg/kg, i.p.) prevented the development of convulsions and brain damage. Neuropathology was observed only in animals that developed repetitive convulsions: the piriform and entorhinal cortex, amygdala, hippocampus and thalamus were the brain structures most consistently damaged. With unilateral injections, the damage was more severe on the side ipsilateral to the injection. The behavioral topography of the convulsions and the neuroanatomical distribution and nature of the subsequent pathology closely resemble that observed with systemic administration of these compounds. The results indicate that the nerve agents are not directly neurotoxic, that peripherally induced hypoxia or anoxia are unlikely mechanisms of the neuropathology, and that the brain damage produced by these compounds is primarily seizure-mediated.