胶质细胞源性营养因子和美金胺对脑室周围白质软化新生大鼠远期预后的影响

Effects of glial cell line-derived neurotrophic factor and memantine on long-term prognosis in neonatal rats with periventricular leukomalacia

摘要:

目的：评估胶质细胞源性营养因子（GDNF）和美金胺对脑室周围白质软化（PVL）新生Sprague-Dawley大鼠远期预后的影响。方法：32只5日龄新生大鼠随机分为假手术（Sham）组、PVL组、GDNF组以及美金胺（Mem）组。除Sham组外，其他3组均行右颈总动脉结扎及缺氧处理（PVL造模）。GDNF组和Mem组分别于造模后即刻注射GDNF 100 μg/kg 和Mem 20 mg/kg。每天对各组大鼠称重。于26日龄（造模后21 d）对各组大鼠进行Morris水迷宫测试及Rivlin斜板实验，记录水迷宫测试时的逃逸潜伏期（escape latency，EL）和游泳距离以及斜板测试时在斜板上至少停留5 s的最大倾斜角度。结果：术后PVL组大鼠的平均体重明显低于Sham组和两个用药组（P<0.05）；EI值和游泳距离均较Sham组和两个用药组显著延长（P<0.05或<0.01）；在斜板上至少停留 5 s 的最大倾斜角度明显低于Sham组和两个用药组（P＜0.05）。两个用药组和Sham组在体重、EI和游泳距离以及斜板的最大倾斜角度之间的差异均无统计学意义。结论：GDNF和Mem均可增强PVL大鼠的空间辨识、学习记忆和运动协调能力，促进体重增长，明显改善远期预后。

Abstract:

OBJECTIVE: To evaluate the effects of glial cell line-derived neurotrophic factor (GDNF) and memantine on the longterm prognosis in neonatal rats with ischemia-induced periventricular leukomalacia (PVL). METHODS: Thirty-two 5-day-old neonatal rats were randomly divided into 4 groups: sham-operated, PVL, GDNF-treated and memantine-treated. PVL was induced by right carotid artery ligation and hypoxia in the PVL, GDNF-treated and memantine-treated groups. GDNF (100 μg/kg) or memantine (20 mg/kg) was injected in the two treatment groups immediately after PVL inducement. The weight of the rats was measured immediately before and after hypoxia ischemia (HI). Both of Morris water maze test and Rivlin inclined plane test were performed at 26 days old (21 days after HI). The values of the escape latency (EL) and swimming distance, and the maximum inclined plane degree which the rats could stand at least 5 seconds were compared among the four groups. RESULTS: The lower weight, the prolonged mean values of EL and swimming distance and the reduced maximum inclined plane degree were observed in the PVL group compared to those in the sham-operated, GDNF-treated and memantine-treated groups. There were no significant differences in the weight, the values of EI and swimming distance and the maximum inclined plane degree between the two treatment groups and the sham-operated group. CONCLUSIONS: The administration of either GDNF or memantine can markedly increase the abilities of spatial discrimination, learning and memory, and motor coordination, promote weight gain, and improve long-term prognosis in rats with PVL.