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异氟烷诱导成年大鼠海马细胞损伤和认知功能障碍。

Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats.

机构信息

Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.

出版信息

Neuropharmacology. 2011 Dec;61(8):1354-9. doi: 10.1016/j.neuropharm.2011.08.011. Epub 2011 Aug 16.

DOI:10.1016/j.neuropharm.2011.08.011
PMID:21864548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3189329/
Abstract

Post-operative cognitive dysfunction (POCD) is a clinical phenomenon characterized with cognitive decline in patients after anesthesia and surgery. It has been shown that interleukin-1β (IL-1β) contributes to the cognitive impairment of mice after surgery and isoflurane anesthesia. This study is designed to determine whether isoflurane alone increases inflammatory cytokines and causes cell injury and cognitive impairment. Four-month-old male Fisher 344 rats were exposed to or were not exposed to 1.2% isoflurane for 2 h. Two weeks later, rats were subjected to Barnes maze and fear conditioning tests. Although animals exposed to or non-exposed to isoflurane developed spatial learning, animals exposed to isoflurane had significant impairments in long-term spatial memory assessed by Barnes maze. They also had impaired hippocampus-dependent learning and memory in fear conditioning test. IL-1β in the hippocampus was increased at 6 h after isoflurane exposure. Isoflurane also increased activated caspase 3 in the hippocampus and decreased the neuronal density in the CA1 region. However, isoflurane did not change the amount of β-amyloid peptide in the cerebral cortex at 29 days after isoflurane exposure when cognitive impairment was present. These results suggest that isoflurane increases inflammatory cytokine expression and causes cell injury in the hippocampus, which may contribute to isoflurane-induced cognitive impairment in rats.

摘要

术后认知功能障碍(POCD)是一种临床现象,其特征是麻醉和手术后患者的认知能力下降。已经表明白细胞介素-1β(IL-1β)有助于手术后和异氟烷麻醉的小鼠的认知障碍。本研究旨在确定异氟烷单独是否会增加炎症细胞因子并导致细胞损伤和认知障碍。四个月大的雄性 Fisher 344 大鼠暴露于或不暴露于 1.2%异氟烷 2 小时。两周后,大鼠进行 Barnes 迷宫和恐惧条件反射测试。尽管暴露于或不暴露于异氟烷的动物均表现出空间学习能力,但暴露于异氟烷的动物在 Barnes 迷宫测试中表现出明显的长期空间记忆障碍。它们在恐惧条件反射测试中也表现出海马体依赖的学习和记忆受损。异氟烷暴露后 6 小时,海马体中的 IL-1β 增加。异氟烷还增加了海马体中活化的 caspase 3,并减少了 CA1 区的神经元密度。然而,当认知障碍存在时,异氟烷在异氟烷暴露 29 天后并未改变大脑皮层中β-淀粉样肽的含量。这些结果表明,异氟烷增加了海马体中炎症细胞因子的表达并导致细胞损伤,这可能导致大鼠异氟烷诱导的认知障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/891d8acb7edf/nihms321675f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/4c7762ac88e9/nihms321675f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/891d8acb7edf/nihms321675f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/4c7762ac88e9/nihms321675f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/88b15dc1e617/nihms321675f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e71/3189329/6fc242c643a7/nihms321675f3.jpg
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