Institut de Recherche Biomédicale des Armées (IRBA), Place Général Valérie André, BP 73, 91223 Brétigny-sur-Orge Cedex, France.
Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, CNRS UMR 5287, 33615 Pessac, France.
Toxicol Lett. 2018 Sep 1;293:73-76. doi: 10.1016/j.toxlet.2017.07.889. Epub 2017 Jul 22.
Cognitive and emotional disorders have been reported in veterans intoxicated with sulfur mustard (SM) a chemical weapon belonging to the category of vesicating agents. However, the intense stress associated with the SM intoxication may render difficult determining the exact role played by SM intoxication itself on the emergence and maintaining of cognitive disorders. Animal's model would allow overcoming this issue. So far, we presently investigated the cognitive and emotional impact of an acute cutaneous intoxication with CEES (2-chloroethyl ethyl sulfide), a SM analog in C57/Bl6 mice. Our study evidenced that up to 5days after a single acute neat CEES skin exposure, compared to controls, mice exhibited i) a significant increase in anxiety-like reactivity in an elevated plus-maze and in an open-field tasks and ii) an alteration of working memory in a sequential alternation task. In contrast, mice submitted to intoxication with a diluted CEES solution or hydrochloric acid (HCl) did not show any memory or emotional impairments. Given that, Our data shows that a single local cutaneous intoxication with neat CEES induced long-lasting cognitive and emotional pejorative effects, in accordance with the epidemiological observations in veterans. Thus, the single acute neat CEES cutaneous intoxication in mice could allow studying the sulfur mustard-induced cognitive and emotional disorders and their further counter-measures.
认知和情绪障碍已在芥子气（SM）中毒的退伍军人中报告，芥子气是一种属于糜烂性毒剂类别的化学武器。然而，与 SM 中毒相关的强烈压力可能使得难以确定 SM 中毒本身对认知障碍的出现和维持的确切作用。动物模型将克服这个问题。到目前为止，我们在 C57/Bl6 小鼠中研究了急性皮肤接触 CEES（2-氯乙基乙基硫醚），一种 SM 类似物对认知和情绪的影响。我们的研究表明，与对照组相比，在单次急性纯 CEES 皮肤暴露后长达 5 天，小鼠表现出：i）在高架十字迷宫和旷场任务中焦虑样反应明显增加；ii）在连续交替任务中工作记忆改变。相比之下，接受稀释的 CEES 溶液或盐酸（HCl）中毒的小鼠没有表现出任何记忆或情绪障碍。鉴于此，我们的数据表明，单次局部皮肤接触纯 CEES 会导致长期的认知和情绪恶化，这与退伍军人中的流行病学观察结果一致。因此，单次急性纯 CEES 皮肤接触在小鼠中可能允许研究芥子气引起的认知和情绪障碍及其进一步的对策。
