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脂多糖诱导的小鼠谵妄样行为和小胶质细胞激活与脑电双频指数相关。

Lipopolysaccharide-Induced Delirium-Like Behavior and Microglial Activation in Mice Correlate With Bispectral Electroencephalography.

机构信息

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.

Department of Neuropsychiatry, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.

出版信息

J Gerontol A Biol Sci Med Sci. 2024 Dec 1;79(12). doi: 10.1093/gerona/glae261.

Abstract

Delirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an lipopolysaccharide-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an lipopolysaccharide-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.

摘要

谵妄是一种多因素的医学病症,表现为各种精神功能受损,是导致住院时间延长、发病率和死亡率增加的最大危险因素之一。由于缺乏用于诊断患者的客观措施,针对谵妄的研究一直具有挑战性,并且很少有实验室模型得到验证。我们最近的研究报告了双谱脑电图(BSEEG)在诊断患者谵妄和预测患者预后方面的功效。我们应用 BSEEG 验证了脂多糖诱导的谵妄小鼠模型。此外,我们还研究了 BSEEG 评分、年轻和老年小鼠海马齿状回和皮质区域的类谵妄行为以及小胶质细胞激活之间的关系。在年轻小鼠中,BSEEG 评分与注意力障碍之间存在显著相关性。此外,在年轻和老年小鼠的海马齿状回和皮质区域中,BSEEG 评分与小胶质细胞激活之间存在显著相关性。我们通过显示 BSEEG 方法与脂多糖诱导的谵妄小鼠模型中的行为变化和小胶质细胞激活水平相关联,成功验证了 BSEEG 方法。此外,BSEEG 方法能够敏感地捕捉到由于低反应状态而行为测试无法捕捉到的脂多糖诱导的类谵妄状态。

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