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

Tsuyoshi Nishiguchi, Kyosuke Yamanishi, Nipun Gorantla, Akiyoshi Shimura, Tomoteru Seki, Takaya Ishii, Bun Aoyama, Johnny R Malicoat, Nathan James Phuong, Nicole Jade Dye, Takehiko Yamanashi, Masaaki Iwata, Gen Shinozaki
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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.

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LPS 诱导的小鼠谵妄样行为和小胶质细胞活化与双谱脑电图 (BSEEG) 相关。
谵妄是一种多因素疾病,其特点是各种精神功能受损,是导致长期住院、发病和死亡的最大风险因素之一。由于缺乏对患者进行诊断的客观测量方法,而且很少有实验室模型经过验证,因此以谵妄为重点的研究已被证明具有挑战性。我们最近的研究报告显示,双谱脑电图(BSEEG)在诊断患者谵妄和预测患者预后方面具有疗效。我们应用 BSEEG 验证了脂多糖(LPS)诱导的小鼠谵妄模型。此外,我们还研究了 BSEEG 评分、谵妄样行为以及年轻小鼠和老年小鼠海马齿状回和皮层区域小胶质细胞活化之间的关系。在年轻小鼠中,BSEEG 评分与注意力受损之间存在明显的相关性。此外,年轻小鼠和老年小鼠的 BSEEG 评分与海马齿状回和皮层区域的小胶质细胞活化之间存在显著相关性。在 LPS 诱导的小鼠谵妄模型中,我们成功验证了 BSEEG 方法与行为变化和小胶质细胞活化水平的相关性。此外,BSEEG 方法还能灵敏地捕捉到 LPS 诱导的类似谵妄的状态,而行为测试由于低活性状态而无法捕捉到这种状态。
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