运动康复对缺氧缺血性脑损伤新生大鼠空间学习记忆的影响

Physical training improves spatial learning and memory impairments following hypoxic-ischemic brain damage in neonatal rats

目的探讨运动康复对缺氧缺血性脑损伤(HIBD)新生大鼠脑结构和空间学习记忆的影响。方法 48只7日龄Sprague-Dawley大鼠随机分为假手术组、HIBD组及运动组。HIBD组和运动组建立HIBD模型,运动组于建模2周后开始4周的运动康复。检测各组大鼠运动功能和空间学习记忆能力,观察脑重变化和突触超微结构,计数海马CA1区存活锥体细胞并检测磷酸化CaMKII及脑源性神经营养因子(BDNF)表达水平。结果运动组大鼠运动功能及空间学习记忆能力均优于HIBD组,和假手术组间差异无统计学意义。HIBD组大鼠海马突触前膜囊泡减少,突触间隙增宽,突触后致密物变薄,而运动组未见明显异常。HIBD组、运动组大鼠左侧脑重及海马CA1区存活锥体细胞均较假手术组低,HIBD组又较运动组低(P<0.01)。运动组大鼠海马CA1区磷酸化CaMKII和BDNF表达水平均明显高于HIBD组。结论运动康复可促进HIBD大鼠海马神经元存活,增强突触可塑性,改善其受损的空间记忆能力。

Objective To investigate the effect of physical training on cerebral structure and spatial learning and memory in neonatal rats submitted to hypoxic-ischemic brain damage（HIBD）.Methods Forty-eight 7-day-old Sprague-Dawley rats were randomly divided into three groups： a group that was subjected to left carotid ligation followed by 2 hrs hypoxic stress（HIBD）;a group that received physical training 2 weeks after the HIBD event;a control group that was subjected to a sham-operation without ligation and hypoxic stress.Following four weeks physical training,motor function test and water maze tasks were performed.Bilateral brain weight,cerebral morphology and left hippocampal ultrastructrue of the animals were examined.The expression levels of phosphor calmodulin-dependent protein kinase II（CaMKII） and brain derived neurotrophic factor（BDNF） were determined by immunohistochemistry.Results Compared with the control group,the motor function and the spatial learning and memory ability in the non-trained HIBD group were significantly decreased,whereas there was no significant difference between the trained-HIBD and the control groups.The left hemisphere weight and neurons in the left hippocampal CA1 zone of both HIBD groups decreased and the reduction was more significant in non-trained HIBD group.The ultrastructure of the left hippocampus was remarkably abnormal in the non-trained HIBD group,while no obvious abnormality was observed in the trained HIBD and the control groups.Phosphor-CaMKII and BDNF expression in the left hippocampus in the trained HIBD group increased significantly compared with that in the non-trained HIBD group.Conclusions Physical training can restrain brain damage and ameliorate spatial learning and memory impairments in rats with HIBD.