早期环境刺激对缺氧缺血性脑损伤大鼠学习记忆的影响

Effects of environmental stimulation on learning and memory in young rats with hypoxic-ischemia brain damage

目的探讨生命早期丰富环境和触摸干预对缺氧缺血性脑损伤(HIBD)大鼠空间参考学习记忆能力及海马CA1区神经元数量的影响。方法生后7 d大鼠,建立HIBD动物模型,随机分为未干预组、丰富环境组、早期触摸组、联合干预组;另设假手术组,每组各14只大鼠。HIBD后7 d开始给予大鼠不同干预,于生后35 d行Morris水迷宫测试;同时,采用尼氏染色法观察各组大鼠海马CA1区神经元数量的变化。结果在Morris水迷宫隐蔽平台测试中,丰富环境组和联合干预组大鼠到达平台的平均潜伏期时间明显短于未干预组和早期触摸组,差异有统计学意义(P均<0.05);而早期触摸组与未干预组的差异无统计学意义。在Morris水迷宫探索测试中,丰富环境组和联合干预组大鼠在目标象限停留的百分比较未干预组显著增高,差异有统计学意义(P均<0.01),而早期触摸组和未干预组的差异无统计学意义。HIBD大鼠损伤侧海马CA1区神经元较假手术组明显减少,差异有统计学意义(P<0.001);其中联合干预组和丰富环境组大鼠损伤侧海马CA1区神经元的数目较未干预组和早期触摸组增加,差异有统计学意义(P<0.05);丰富环境组大鼠非损伤侧神经元数目增加,与其他各组比较差异有统计学意义(P<0.05)。结论新生仔鼠HIBD后1周开始的丰富环境仍可促进仔鼠脑功能恢复;新生仔鼠HIBD后早期短暂的触摸并不能增加丰富环境干预的疗效。

Objective To explore the effects of enriched environment and neonatal handling on the reference learning and memory test and the number of neurons in hippocampal CA1 region in young rats with the hypoxia ischemia brain damage（HIBD）.Methods The HIBD model was established in Sprague-Dawley（SD）rats aged 7 days.Then the HIBD rats were randomly divided into five groups：sham（n = 14）,HIBD（n = 14）,HIBD with enriched environment（HIBDE,n = 14）,HIBD with neonatal handling（HIBDN,n = 14）,HIBD with combined intervention（HIBDC,n = 14）.After 7 days of HIBD,the different interventions were implemented.At 35 days old,the Morris Water Maze test was performed,the number of neurons in hippocampal CA1 was detected by Nissl staining.Results In the Morris water hidden platform test,the latency to the platform in HIBDE and HIBDC were significantly shorter than that in HIBD and HIBDN（P all 0.05）.However,there was no significant difference between HIBD and HIBDN.In the Morris water exploratory test,the percentage of the time in target quadrant in HIBDE and HIBDC were significantly higher than that in HIBD（P all 0.01）.However,there was no significant difference between HIBDN and HIBD.The number of neurons in the damaged side of hippocampus was significantly less in HIBD than that in sham group（P 0.001）.The number of neurons in the damaged side was significantly increased in HIBDC and HIBDE than that in HIBD and HIBDN（P 0.0.5）.The number of neurons in the un-damaged side was significantly increased in HIBDE than that in HIBD,HIBDN and HIBDC（all P 0.05）.Conclusions The enriched environment implemented one week after HIBD could promote the recovery of neonatal rats＇brain damage.The short time neonatal handling immediately after HIBD could not further enhance the effect of enriched environment.