Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
J Pharm Pharmacol. 2012 Feb;64(2):302-7. doi: 10.1111/j.2042-7158.2011.01404.x. Epub 2011 Nov 18.
General anesthetics may contribute to the post-operative cognitive dysfunction. This study was designed to determine the effects of isoflurane on the learning and memory of healthy animals or animals with a decreased brain antioxidative capacity.
Seven- to nine-week-old female CD-1 wild-type mice or glutamate transporter type 3 (EAAT3) knockout mice whose brains have a decreased glutathione level were exposed to or were not exposed to 1.3% isoflurane for 2 h. They were subjected to fear conditioning or Barnes maze tests 1 week later.
The EAAT3 knockout mice had less freezing behaviour than the wild-type mice in tone-related fear. Isoflurane did not affect the freezing behaviour of the wild-type and EAAT3 knockout mice. The time for the wild-type and EAAT3 knockout mice to identify the target hole in the training sessions and memory test with the Barnes maze was not affected by isoflurane. However, the EAAT3 knockout mice took longer to identify the target hole than the wild-type mice in these tests.
These results suggest that EAAT3 knockout mice have significant cognitive impairment. Isoflurane may not significantly affect the cognition of wild-type and EAAT3 knockout mice in a delayed phase after isoflurane exposure.
全身麻醉可能导致术后认知功能障碍。本研究旨在确定异氟醚对健康动物或脑抗氧化能力降低动物的学习和记忆的影响。
7-9 周龄雌性 CD-1 野生型小鼠或谷氨酸转运体 3(EAAT3)敲除小鼠,其大脑中的谷胱甘肽水平降低,暴露于或不暴露于 1.3%异氟醚中 2 小时。1 周后,它们接受恐惧条件反射或 Barnes 迷宫测试。
EAAT3 敲除小鼠在与音调相关的恐惧中比野生型小鼠的冻结行为更少。异氟醚不影响野生型和 EAAT3 敲除小鼠的冻结行为。在训练和 Barnes 迷宫记忆测试中,野生型和 EAAT3 敲除小鼠识别目标孔的时间不受异氟醚的影响。然而,在这些测试中,EAAT3 敲除小鼠识别目标孔的时间比野生型小鼠长。
这些结果表明 EAAT3 敲除小鼠有明显的认知障碍。异氟醚暴露后延迟期,异氟醚可能不会显著影响野生型和 EAAT3 敲除小鼠的认知功能。