Combination treatment of neonatal rats with hypoxia-ischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage
Combination treatment of neonatal rats with hypoxia-ischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage
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DOI：
10.1016/j.ajog.2004.04.039
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发表时间：
2004-12-01
影响因子：
9.8
通讯作者：
Ikenoue, T
中科院分区：
文献类型：
--
作者：
Ikeda, T;Mishima, K;Ikenoue, T
目的：我们利用行为任务和脑组织学结果评估围产期缺氧缺血和内毒素对新生大鼠注意力和短期和长期记忆的长期影响。研究设计：注射脂多糖（1 mg/kg，腹腔注射）或盐溶液4小时后，7日龄Wistar幼鼠进行单侧缺氧缺血1小时。我们研究了 4 组：对照组（n = 43 只大鼠）、单独脂多糖组（n = 12 只大鼠）、单独缺氧缺血组（n = 29 只大鼠）以及脂多糖 + 缺氧缺血联合治疗组（n = 34 只大鼠）。治疗后 7 至 16 周，我们通过选择反应时间任务测量注意力，通过 8 臂径向迷宫任务测量短期记忆，通过水迷宫任务测量长期记忆。 19周龄时，大脑被取出、固定并进行冠状切片；结果：脂多糖组、缺氧缺血组、脂多糖+缺氧缺血组海马体积减少；在缺氧缺血组和脂多糖+缺氧缺血组中观察到纹状体损失，但仅在脂多糖+缺氧缺血组中观察到皮质损失。在选择反应时任务中，脂多糖组、缺氧缺血组和脂多糖+缺氧缺血组的表现（注意力缺陷）明显较差于对照组。在径向迷宫任务中，与其他组相比，脂多糖+缺氧缺血组的正确选择减少，错误增加，这表明短期记忆受损。在水迷宫测试中，缺氧缺血组和脂多糖+缺氧缺血组的游泳距离显着大于其他两组，这表明长期记忆受损。结论：脂多糖和缺氧缺血联合治疗可协同诱导短期记忆受损，并与皮质体积损失相关。 (C) 2004 Elsevier Inc. 保留所有权利。
Objective: We assessed the long-term effects of perinatal hypoxia-ischemia and endotoxin on attention and short- and long-term memory in neonatal rats with the use of behavioral tasks and brain histologic results.Study design: Four hours after injections of lipopolysaccharide (1 mg/kg, intraperitoneally) or saline solution, 7-day-old Wistar rat pups were subjected to unilateral hypoxia-ischemia for 1 hour. We studied 4 groups: controls (n = 43 rats), lipopolysaccharide alone (n = 12 rats), hypoxia-ischemia alone (n = 29 rats), and combined lipopolysaccharide + hypoxia-ischemia treatment (n = 34 rats). Seven to 16 weeks after the treatment, we measured attention with a choice reaction time task, short-term memory with an 8-arm radial maze task, and long-term memory with a water maze task. At 19 weeks of age, the brain was removed, fixed, and sectioned coronally; and the Volume of each part was measured.Results: A loss of volume in the hippocampus was observed in the lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups; a loss of striatum was observed in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups, but loss of cortex was observed only in the lipopolysaccharide + hypoxia-ischemia group. The lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups showed significantly poorer performance (attention deficit) than controls in the choice reaction time task. Correct choices decreased, and error increased in the lipopolysaccharide + hypoxia-ischemia group compared with the other groups in the radial maze task, which shows short-term memory impairment. Swimming distance was significantly greater in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups than in the other 2 groups in the water maze test, which shows long-term memory impairment.Conclusion: Combined lipopolysaccharide and hypoxia-ischemia treatment synergistically induced short-term memory impairment that is associated with loss of cortical volume. (C) 2004 Elsevier Inc. All rights reserved.