新生大鼠缺氧缺血性脑损伤后的远期行为学测试

目的：目前对新生鼠缺氧缺血性脑损伤(HIBD)模型的研究多采用病理学和生化指标,而缺乏功能评价手段。该研究对新生大鼠HIBD后的行为学改变及其测定方法进行探讨,为新生大鼠HIBD的研究提供功能评价的方法。方法：24只7日龄新生SD大鼠随机分为对照组(n=12)和HIBD组(n=12),HIBD组大鼠予以缺氧缺血,对照组大鼠仅予以假手术。生后3周,两组大鼠予以T迷宫测试及感觉运动测试对学习记忆、空间能力和感觉运动功能进行评估。然后处死两组大鼠,取脑组织切片行尼氏染色,计数海马DG区和皮层区单位面积神经元的数目,并对行为学和组织学的结果进行相关分析。结果：在行为测试中,HIBD组大鼠的成绩显著低于正常鼠。在T迷宫测试中,两组在第3,4d的正确率有显著差异(P=0.049,P<0.001),HIBD组的正确率(68.3%±26.2%,66.7%±15.6%)显著低于对照组(86.7%±15.6%,98.3%±5.7%)。在感觉运动测试中,与正常鼠比较,HIBD鼠在足错误和肢体放置测试中表现出左右运动的不对称(均P<0.001),姿势反射也显示出了运动功能异常(P=0.032)。缺氧缺血导致了神经元损伤,使海马DG区(39.7±5.9vs50.9±4.1,P<0.001)和皮层单位面积内神经元(12.7±3.3vs18.2±3.3,P<0.001)数目显著减少。但行为学测试结果与组织学改变无相关性。结论：新生鼠缺氧缺血会造成远期学习记忆,空间能力和感觉运动功能障碍,T迷宫测试和三项感觉运动测试可以作为大鼠HIBD模型的评价指标。

Long-lasting behavioral alterations in neonatal rats after hypoxic-schemic brain damage

OBJECTIVE: The neonatal rat model of hypoxic-ischemic brain damage (HIBD) is a useful tool for studying hypoxic-ischemic encephalopathy of the newborn. Although many reports have studied the pathological and biochemical outcomes on HIBD in the animal model, little research has focused on assessing the long-lasting behavioral changes. This study was designed to examine the long-lasting behavioral alternations following HIBD in neonatal rats. METHODS: Twenty-four 7-day-old SD rats were randomly assigned into a Control group (n = 12) and a HIBD group (n = 12). The rats in the HIBD group were subjected to ligation of the left carotid artery, followed by 2 hrs hypoxia exposure. A battery of behavioral tests, including the T-maze test and sensorimotor tests, were performed at postnatal age 3 - 4 weeks. Histological changes and their correlations with the results of behavioral tests were evaluated. RESULTS: In the behavioral tests, HIBD rats performed significantly worse than control rats. In the T-maze test, the HIBD group differed significantly from the Control group, achieving the correct percentage on the 3rd and 4th days after hypoxia-ischemia (HI) of 68.3%±26.2% vs 86.7%±15.6% ( P =0.049) and 66.7%±15.6% vs 98.3%±5.7% (P < 0.001), respectively. In the sensorimotor tests, asymmetries of foot-faults and limb-placing were detected in HIBD rats. The postural reflex test showed an abnormal motor function in HIBD rats. The neurons number in the DG area of the hippocampus (39.7 ± 5.9) and the cortex ( 12.7±3.3) was significantly reduced in the HIBD group when compared with those in the Control group (50.9 ± 4.1 and 18.2 ± 3.3, respectively). There was no correlation between the behavioral tests results and histological changes. CONCLUSIONS: HI injury in neonatal rats may cause long-lasting deficits of learning, spatial and sensorimotor function. Behavioral testing is an important measure of outcome following HIBD, and behavioral testing measures may be used to test the efficacy of HIBD treatment.