卡莫司汀致皮质发育障碍的模型研究

Animal models of cortical dysplasia induced by carmustine

目的建立SD大鼠广泛型皮质发育障碍的动物模型。方法在SD大鼠孕17d腹腔注入BCNU（1，3-二氯乙烯一亚硝基脲，卡莫司汀1制作皮质发育障碍模型：病理检查P60仔鼠皮层和海马结构及神经元变化；行为学观察和脑电图检测；热水浴诱导痫性发作．观察两组大鼠的致痫潜伏期和癫痫持续时间；Y迷宫法测试不同时间点仔鼠学习记忆能力。结果P0仔鼠脑组织湿重实验组比对照组显著减轻（P〈0．01）；Nissl染色显示皮质层次紊乱、海马区域异位细胞异常聚集，可出现结节状灰质团块；模型鼠日常活动能力较差，脑电图未见明显痫性放电：模型组热水浴诱导惊厥发作的潜伏期明显缩短（P〈0．011；模型组达到学会标准所需电击次数较对照组增加（P〈0.05）。结论孕17d腹腔注射BCNU可建立广泛型皮质发育障碍的动物模型．其致痫敏感性增加，且伴有认知功能障碍。

Objective To establish the animal model of diffuse cortical dysplasia in Sprague-Dawley rats. Methods Pregnant rats were given intrapefitoneal injections of BCNU on embryonic day 17 （E17）. Cresyl-violet staining was applied to observe the histological changes in the cortex, hippocampus and neurons of the resulted pups at P60. EEG recordings were detected, and daily activities were observed. Hot water bath was used to induce seizures, the latency to seizure onset and duration of SE （epileptic status） were compared. Learning and memory abilities were estimated with Y maze at different time points. Results The mean wet brain weights in the BCNU-exposed pups were lower than those of controls on P0 （P〈0.01）. Cresyl-violet staining revealed disruption of cortical lamination and heterotopic cell clusters within the hippocampus. Daily activities were poor in BCNU-exposed pups. No obvious epilepsia discharges were detected. After being induced seizures, adult rats with cortical dysplasia had shorter latency to seizures（P〈0.01）. The frequency of attempting learning and memory of rats in model group was increased than that in normal group （P〈0.05）. Conclusions Intraperitoneal injections of BCNU on embryonic day 17 （E 17） can establish the animal model of diffuse cortical dysplasia, and this model has increased seizure susceptibilities and cognitive functional impairments.