丰富环境干预促进缺氧缺血性脑损伤新生大鼠神经元细胞增殖和功能修复

Effects of environmental enrichment on the repair and proliferation of neurons in neonatal rats with hypoxic-ischemic brain damage

摘要:

目的：探讨丰富环境刺激对缺氧缺血性脑损伤（HIBD）新生大鼠神经元增殖、学习记忆能力和运动功能的影响。方法：108只7 日龄Sprague-Dawley新生大鼠随机分为假手术组、HIBD组和干预组。采用Rice-Vannucci方法制作HIBD模型。干预组于HIBD后行丰富环境刺激。干预后7 d、14 d、28 d进行行为学测试（水迷宫试验、悬吊试验、斜坡试验），光镜下计数海马CA1区单位面积神经元的数目。结果：HIBD 组7 d、14 d和28 d海马CA1区锥体细胞数明显少于假手术组锥体细胞数（P<0.01）；干预组干预后7 d、14 d和28 d海马CA1区锥体细胞数均多于HIBD组（P<0.01）。HIBD组和干预组7 d、14 d、28 d隐匿平台逃避潜伏期（EL）较假手术组明显延长（P<0.01），跨越平台次数均明显低于假手术组（P<0.01），而干预组7 d、14 d及28 d EL较HIBD组明显缩短，跨越平台次数较HIBD组明显增加（P<0.01）。HIBD 组与干预组7 d、14 d和28 d悬吊试验维持时间和得分均低于假手术组（P<0.01），斜坡试验时间高于假手术组（P<0.01），而干预组14 d和28 d悬吊试验维持时间和得分均明显高于HIBD组（P<0.01），斜坡试验时间明显低于HIBD组（P<0.01）。结论：早期丰富环境干预可以促进HIBD神经细胞的修复，并改善大鼠学习记忆能力和运动功能。

Abstract:

OBJECTIVE: To study the effects of environmental enrichment on neuron proliferation, learning and memory ability and motor ability in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: One hundred and eight 7-day-old Sprague-Dawley rats were randomly divided into three groups: sham operation (CON group), HIBD and intervention group. HIBD model was prepared according to the classic Rice-Vannucci method. Environmental enrichment was administered for the rats in the intervention group after HIBD inducement. Behavioral tests (Water maze test, Suspension test and Slope test) were performed and the number of neural cells in the left hippocampus was examined 7, 14 and 28 days after intervention. RESULTS: The pyramid cells in the hippocampus CA1 area in the HIBD group were significantly less than in the CON group at 7, 14 and 28 days (P<0.05). The number of pyramid cells in the hippocampus CA1 area in the intervention group was significantly higher than in the HIBD group (P<0.01) at 7, 14 and 28 days. The hidden platform escape latency period (EL) in the Water maze test was significantly more prolonged and the cross-platform number within 2 minutes was significantly less in the HIBD and the intervention groups than in the CON group at all observed time points (P<0.01). The EL was significantly shorter and the cross-platform number within 2 minutes was significantly higher in the intervention group than in the HIBD group at all observed time points (P<0.01). The maintain time and score in the Suspension test were significantly lower and the time in the Slope test was significantly more prolonged in the HIBD and intervention groups than in the CON group at 7, 14 and 28 days (P<0.01). An increased maintain time and score and a decreased time in the Slope test were found in the intervention group compared with the HIBD group at 14 and 28 days (P<0.01). CONCLUSIONS: Environmental enrichment can improve motor function, learning and memory ability, and promote the repair and proliferation of neurons in neonatal rats with HIBD.