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Behavioral alterations following a hypoxic-ischemic brain injury in neonatal rats and the effects of treatment with caspase inhibitor.

新生大鼠缺氧缺血性脑损伤后的行为改变以及半胱天冬酶抑制剂治疗的效果。

基本信息

批准号：
13671136
负责人：
TAKADA Satoshi
金额：
$ 2.3万
依托单位：
Kobe University. School of Medicine, Faculty of Health Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain following hypoxic-ischemic (HI) insult. The characterization of motor and cognitive dysfunctions following neonatal ischemic injury was assessed by using Moris water maze test. Furthermore we investigated the effect of caspase inhibitor administration on the cognitive alterations following HI insult.1) Behavioral alterations following a hypoxic-ischemic brain injuryHI model animals were obtained by the combination of monolateral carotid ligation and exposure to 8 % oxygen for 2 hours in 7-day-old rats. The animals were tested in a water maze test at 28 days old. No significant differences were found between ischemic and control rats in the speed of swimming. The average latency for HI rats to reach the fixed platform was significantly prolonged in comparison with control rats, and the ischemic group rats were unable to perform the test without mistakes.2) The relation between the histological findings and learning abilityThe extend of the brain damage was not the same in all ischemic animals. The number of neuronal cells in the ipsilateral hippocampal CA1 region was counted. There was no significant relation between the histological findings and the extend of behavioral alternations statistically.3) The effects of caspase inhibitor (BAF) on the behavioral alternationsBAF was injected intraperitoneally after HI loading. No significant effect in learning ability was observed in BAF treated rats.

Caspase被认为在缺氧缺血（HI）损伤后大鼠脑中观察到的迟发性神经元细胞死亡中起关键作用。采用Moris水迷宫试验评估新生儿缺血性损伤后运动和认知功能障碍的特征。此外，我们研究了半胱天冬酶抑制剂给药对HI损伤后认知改变的影响。1）缺氧缺血性脑损伤后的行为改变通过将7日龄大鼠单侧颈动脉结扎和暴露于8%氧气2小时相结合来获得HI模型动物。在28日龄时在水迷宫测试中测试动物。缺血组和对照组大鼠的游泳速度无显著差异。HI组大鼠到达固定平台的平均潜伏期较对照组明显延长，缺血组大鼠不能准确无误地完成实验。2）组织学表现与学习能力的关系所有缺血动物的脑损伤程度不同。计数同侧海马CA1区神经元细胞数。组织学检查结果与行为学改变程度无明显相关性。3）caspase抑制剂（BAF）对行为学改变的影响HI负荷后腹腔注射BAF。在BAF处理的大鼠中未观察到对学习能力的显著影响。