Long-term cognitive impairment and myelination deficiency in a rat model of perinatal hypoxic-ischemic brain injury
Long-term cognitive impairment and myelination deficiency in a rat model of perinatal hypoxic-ischemic brain injury
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DOI：
10.1016/j.brainres.2009.09.006
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发表时间：
2009-11-16
期刊：
影响因子：
2.9
通讯作者：
Chen, Chao
中科院分区：
文献类型：
--
作者：
Huang, Zhiheng;Liu, Jiangqin;Chen, Chao
虽然脑室周围白质损伤是早产儿主要神经功能障碍的主要原因，但髓鞘形成缺陷与长期认知功能障碍之间的关系尚不清楚。本研究旨在探讨围产期缺氧缺血(HI)大鼠少突胶质细胞髓鞘形成和长期空间认知功能的变化。出生后第3天(P3)大鼠结扎右侧颈动脉，然后低氧(6%氧气)2.5h。分别于伤后6天(伤后72小时)和伤后47天进行脑损伤早期和晚期的免疫组织化学染色。用Morris水迷宫测试评估P42时的空间认知功能，然后进行组织学评估。与对侧和假手术对照组相比，损伤后72小时，HI引起同侧白质中少突胶质细胞前、星形胶质细胞和小胶质细胞的增加(均P<；0.05)。与对侧脑室周围白质和假手术对照组相比，髓鞘碱性蛋白(MBP)和2‘，3’-环核苷酸T-磷酸二酯酶(CNPase)标记的胶质纤维酸性蛋白(GFAP)标记的少突胶质细胞在P47时明显减少(均P<0.05)。与假手术对照组相比，HI大鼠在航行试验中存在空间学习障碍(较长的逃避潜伏期和游泳距离)，在探测试验中出现记忆障碍(跨越平台的次数和停留在目标象限的时间百分比较少)(p
Although periventricular white matter injury is a leading cause of major neurologic disability in premature infants, the relationship between myelination deficiency and long-term cognitive dysfunction is not well understood. The purpose of this study was to investigate oligodendrocytes myelination and long-term spatial cognitive function in rats with perinatal hypoxia-ischemia (HI). Postnatal day 3 (P3) rats were subjected to right carotid artery ligation followed by 2.5 h of hypoxia (6% oxygen). Brain injury during the early and late phases was evaluated by immunostaining at P6 (72 h after the injury) and P47. Spatial cognitive function was evaluated at P42 using the Morris Water Maze test followed by histologic evaluation. HI caused an increase in pre-oligodendrocytes, astrocytes, and microglia in the ipsilateral white matter 72 h after the insult compared to contralateral regions and sham-operated controls (both p < 0.05). There were significant decreases in myelin basic protein (MBP)and 2',3'-cyclic nucleotide T-phosphodiesterase (CNPase)-labeled oligodendrocytes with glial fibrillary acidic protein (GFAP)-labeled glial scarring in the ipsilateral periventricular white matter at P47 compared to contralateral regions and sham-operated controls (all p < 0.05). The rats with HI had spatial learning deficits in navigation trials (longer escape latency and swimming distance) and memory dysfunction in probe trials (fewer number of platform crossings and percentage of time in the target quadrant) compared with sham-operated controls (p