环境刺激对缺氧缺血性脑损伤新生大鼠脑功能的影响

Environmental stimulation improves functional deficits induced by hypoxic-ischemic brain damage in neonatal rats

目的 探讨环境刺激对缺氧缺血性脑损伤 (hypoxic ischemicbraindamage,HIBD)新生大鼠脑功能的影响。方法 选用 7日龄雄性SD大鼠 5 1只 ,其中 36只通过结扎右侧颈总动脉 ,吸入氧体积浓度为 (8 0± 0 5 ) %的氮氧混合气体 ,制作新生大鼠HIBD模型 ,制模后的大鼠分为干预组和非干预组 ;正常对照组大鼠 15只 (假手术动物 )。采用早期触摸 (neonatalhandling)和丰富环境 (enrichedenvironment)刺激进行干预 ,干预时间为 30d ,干预结束后进行感觉运动功能 (悬吊试验、行走试验 )和行为检测 (三等分迷宫试验 )以判断干预效果。结果 非干预组大鼠分辨学习能力较干预组和正常对照组差 (P <0 0 1) ,达到学会标准所需的训练次数分别为 :非干预组 (4 5± 9)次、干预组 (2 7± 5 )次、正常对照组 (2 4± 8)次 ;非干预组大鼠感觉运动功能低于干预组和正常对照组 (P <0 0 1) ,悬吊试验时间分别为非干预组 (15± 3)s、干预组 (2 2± 4)s、正常对照组 (36± 6 )s;行走试验时间分别为 (7 0± 1 1)s、(4 0± 0 8)s、(4 0± 0 5 )s;干预组和非干预组大鼠大脑皮层死亡细胞百分数分别为 (35 7± 8 9) %和 (39 1± 10 9) % ,海马部位分别为 (38 5± 6 3) %和 (39 3± 10 4) % 。

Objective Hypoxic-ischemic brain damage (HIBD) in neonatal rats may induce sensorimotor functional and behavioral deficits. It was found that environmental stimulation could influence brain structure and function, and play an important role during brain development. Environmental stimulation can also improve the functional outcome of cerebral infarction in adult rats. The purpose of present study was to observe the influence of environmental stimulation on functional outcome of HIBD in neonatal rats. Methods Seven days old postnatal male SD rats (n=51) were used in this study. HIBD models (n=36) were established as follows: the right common carotid artery was dissected and ligated. After 4 h of recovery, the litters were exposed to 8% oxygen-92% nitrogen gas mixture for 2 h. The HIBD rats were randomly divided into two groups: intervention group and non-intervention group. The sham-operation rats were served as normal control group. Seven rats died during the hypoxic procedure and 5 rats died later. Intervention group (n=12) received the neonatal handling and was kept in an enriched environment for 30 days. Non-intervention group (n=14) and control group (n=13) were kept in a standard condition without the neonatal handling and enriched environment. One behavioral task (discrimination learning in tri-equal-arm maze) and 2 sensorimotor functional tests (suspension test and beam-walking test) were used to evaluate the functional outcome. The extent of brain damage in sensorimotor cortex and hippocampus were assessed histologically at last. Results The numbers of trails to reach the learning criterion were 45±9, 27±5 and 24±8 for non-intervention, intervention and control groups, respectively. The learning ability of non-intervention group reduced and was much lower than those of intervention group and control group (P<0.01). The sensorimotor function of non-intervention group was also lower than those of intervention group and control group (P<0.01). In the suspension test, the time necessary for hanging on to the rope was (15±3) s in the non-intervention group as compared with (22±4) s in the intervention group and (36±6) s in the control group. In the beam-walking test, the time crossed the beam for non-intervention group was (7.0±1.1) s, while for intervention group and control group were (4.0±0.8) s and (4.0±0.5) s, respectively. The percentage of dead neurons in intervention group was (35.7±8.9)% in cortex and (38.5±6.3)% in hippocampus compared with (39.1±10.9)% and (39.3±10.4)%. There was no significant difference with regard to the degree of brain damage between intervention group and non-intervention group (P>0.05). However, there was a positive correlation between behavioral test and the extent of hippocampus damage (r=0.915, P<0.01). Sensorimotor function was correlated with the degree of cortic damage (P<0.01). Conclusion The environmental stimulation can improve the sensorimotor functional outcome and the discrimination learning ability of neonatal rats with HIBD.