通过双谱脑电图发现治疗感染相关谵妄的新型保护剂。

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-03 DOI:10.1038/s41398-024-03130-4
Tsuyoshi Nishiguchi, Kyosuke Yamanishi, Shivani Patel, Johnny R Malicoat, Nathan James Phuong, Tomoteru Seki, Takaya Ishii, Bun Aoyama, Akiyoshi Shimura, Nipun Gorantla, Takehiko Yamanashi, Masaaki Iwata, Andrew A Pieper, Gen Shinozaki
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引用次数: 0

摘要

谵妄是一种多因素的医学症状,随着时间的推移,精神功能的各个领域都会出现损伤。重要的是,谵妄也是导致长期住院、发病和死亡的最大风险因素之一。由于难以对患者进行客观诊断,也难以对实验室模型进行验证,因此研究这一重要病症极具挑战性。因此,目前还缺乏针对谵妄的保护性治疗方法。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,从而推进了这一简单测量可代表患者额外生命体征的概念。在这里,我们应用 BSEEG 鉴定和验证了一种新型感染相关谵妄脂多糖(LPS)小鼠模型。然后,我们应用该模型评估了三种假定治疗药物的保护效力:传统抗精神病药物氟哌啶醇、神经保护化合物 P7C3-A20 和抗生素米诺环素。老年小鼠比年轻小鼠更容易受到LPS诱导的BSEEG畸变的影响,这让人联想到老年人更容易出现谵妄。无论是年轻小鼠还是老年小鼠,服用 P7C3-A20 和米诺环素都能防止 LPS 诱导的 BSEEG 异常。与此相反,氟哌啶醇却不能。P7C3-A20 和米诺环素已被证明能从不同方面限制 LPS 的毒性,我们的数据证明了这些药物可能有助于保护患者免于发生与感染相关的谵妄。因此,在感染相关谵妄的小鼠模型中利用 BSEEG 可以确定可应用于患者临床试验的治疗药物。
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Discovery of novel protective agents for infection-related delirium through bispectral electroencephalography.

Delirium is a multifactorial medical condition of waxing and waning impairment across various domains of mental functioning over time. Importantly, delirium is also one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Studying this important condition is challenging due to the difficulty in both objective diagnosis in patients and validation of laboratory models. As a result, there is a lack of protective treatments for delirium. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes, advancing the concept that this simple measure could represent an additional vital sign for patients. Here, we applied BSEEG to characterize and validate a novel lipopolysaccharide (LPS) mouse model of infection-related delirium. We then applied this model to evaluate the protective efficacy of three putative therapeutic agents: the conventional antipsychotic medication haloperidol, the neuroprotective compound P7C3-A20, and the antibiotic minocycline. Aged mice were more susceptible than young mice to LPS-induced aberration in BSEEG, reminiscent of the greater vulnerability of older adults to delirium. In both young and old mice, P7C3-A20 and minocycline administration prevented LPS-induced BSEEG abnormality. By contrast, haloperidol did not. P7C3-A20 and minocycline have been shown to limit different aspects of LPS toxicity, and our data offers proof of principle that these agents might help protect patients from developing infection-related delirium. Thus, utilization of BSEEG in a mouse model for infection-related delirium can identify putative therapeutic agents for applications in patient clinical trials.

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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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