N-甲基-D-天门冬氨酸(NMDA)诱导幼鼠痫样发作的特征与评价

Characteristics and Evaluation on N-Methyl-D-Asparate Induced Epileptic Seizure in Infant Rats

目的探讨N-甲基-D-天门冬氨酸（NMDA）诱导幼鼠痫样发作的特征,并评价它与人类婴儿痉挛症的异同.方法实验一：24只乳鼠随机分为对照组和实验组,注射不同剂量NMDA,观察行为变化及最佳NMDA剂量.实验二：30只18天乳鼠随机分为对照组和实验组,于不同时间点注射NMDA（45mg/kg）,观察发作高峰期并记录头皮脑电图.实验三：6只乳鼠分别于生后18～30天腹腔注射NMDA（45mg/kg）,观察慢性点燃模型建立情况.实验四：4只成鼠及4只乳鼠分别腹腔注射NMDA, 观察NMDA引起的癫痫发作是否具有年龄依赖性.结果不同剂量的NMDA均可诱导乳鼠出现特异的屈曲样痉挛发作,发作期脑电图出现节律紊乱,表现为高幅慢波,夹有棘波.18天的幼鼠需要的最佳NMDA剂量为45mg/kg,该量处理后20～40分钟为发作高峰. 乳鼠连续腹腔注射NMDA至生后27天开始无特异的屈曲样痉挛发作. 成鼠腹腔注射NMDA后不出现特异的屈曲样痉挛发作.结论 Wistar乳鼠经腹腔注射NMDA,其行为学表现与人类婴儿痉挛症的临床发作极为相似,提示可以作为一种建立婴儿痉挛症动物模型的方法.

Objective To discuss the characteristics of N-methyl-D-asparate （NMDA） induced epileptic seizures in Wistar infant rats, and to evaluate the similarities and differences between it and human infantile spasms（IS）. Method Experiment Ⅰ ：24 infant rats were divided into treatment groups and control group randomly. Normal saline（NS） was administrated to the control group, and different dose of NMDA was administrated to treatment groups. Subsequent behavioral changes and optimal NMDA dose were observed. Experiment Ⅱ：30 infant rats of PN 18 were divided into treatment groups and control group randomly. NS was administrated to the control group ,and NMDA（45mg/kg） was administrated to treatment groups at different time points. The peak period of attack was observed and the scalp electroencephalogram was recorded. Experiment Ⅱ1：6 infant rats were intraperitoneally injected with 45mg/kg of NMDA from PN 18 to PN 30 respectively. The establishment of chronic kindling model was observed. Experiment Ⅳ ：4 adult rats and 4 infant rats received intraperitoneal injection of NMDA respectively, in order to observe if NMDA induced seizure had age-dependence. Results Difference dose of NMDA might induce infant rats to present specific flexion spasms. During attack period,the electroencephalogram presented high amplitude slow wave and acanth wave with rhythm disorder. The optimal NMDA dose of infant rats of PN 18 is 45mg/kg. The attack peak occurred at 30 -40 minutes after NMDA administration. Non-specific flexion spasms began in infant rats after continuous intraperitoneal injection of NMDA till PN 27. However, no adult rats presented specific flexion spasms after intraperitoneal injection of NMDA. Conclusions After intraperitoneal injection of NMDA, the behavioral performance of Wistar infant rats is quite similar to the clinical attack of human infantile spasms,which implies that NMDA can be used as a method to establish an animal model for infantile spasms.