Beneficial effects of enriched environment following status epilepticus in immature rats

Beneficial effects of enriched environment following status epilepticus in immature rats
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DOI:
10.1212/01.wnl.0000033588.59005.55
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发表时间:
2002-11-12
期刊:
影响因子:
9.9
通讯作者:
Holmes, GL
Holmes, GL
中科院分区:
医学1区
文献类型:
--
作者:
Faverjon, S;Silveira, DC;Holmes, GL

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背景资料:越来越多的证据表明,丰富的环境可以改善各种脑损伤后的认知和运动缺陷。环境丰富是否可以改善癫痫持续状态(SE)后的认知障碍尚不清楚。目的:探讨饲养环境对正常大鼠和SE大鼠认知功能的影响。研究方法:大鼠(n = 100)在出生后(P)第20天接受锂-匹鲁卡品诱导的SE,然后置于由玩具、攀爬物体和音乐组成的大型游戏区或标准动物饲养笼中30天。对照大鼠(n = 32)的处理与SE大鼠相似,但接受盐水注射,而不是锂-毛果芸香碱。然后在水迷宫中测试大鼠,这是一种视觉空间记忆的测量方法。一个子集的大鼠在暴露于丰富或非丰富的环境中被杀死,并使用溴脱氧尿苷(BrdU)和磷酸化环磷酸腺苷反应元件结合蛋白(pCREB)免疫染色,一个重要的长期记忆的脑转录因子,检查大脑的齿状颗粒细胞神经发生。结果:对照组和暴露于丰富环境的SE大鼠在水迷宫中的表现均显著优于非丰富组。与非富集组相比,暴露于富集环境的对照组和SE动物的齿状回神经发生和pCREB免疫染色显著增加。环境富集没有导致SE诱导的组织学损伤的变化。结论:暴露于丰富的环境中,断奶大鼠的视觉空间学习显着提高。即使在SE之后,丰富的环境也会增强认知功能。神经发生的增加和转录因子的激活可能有助于这种增强的视觉空间记忆。
Background: There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. Objective: To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Methods: Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Results: Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Conclusions: Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.