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

Overview

Journal J Gerontol A Biol Sci Med Sci

Specialty Geriatrics

Date 2024 Nov 4

PMID 39492697

Authors

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

Affiliations

Soon will be listed here.

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.

References

Wahl D, Coogan S, Solon-Biet S, de Cabo R, Haran J, Raubenheimer D . Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia. Clin Interv Aging. 2017; 12:1419-1428. PMC: 5598548. DOI: 10.2147/CIA.S145247. View

Machado C, Reis-Silva T, Lyra C, Felicio L, Malnic B . Buried Food-seeking Test for the Assessment of Olfactory Detection in Mice. Bio Protoc. 2021; 8(12):e2897. PMC: 8275211. DOI: 10.21769/BioProtoc.2897. View

Inouye S . The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med. 1994; 97(3):278-88. DOI: 10.1016/0002-9343(94)90011-6. View

Altman J, Das G . Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol. 1965; 124(3):319-35. DOI: 10.1002/cne.901240303. View

Zarei K, Sparr N, Trapp N, Neuhaus E, Cromwell J, Boes A . Bispectral EEG (BSEEG) to assess arousal after electro-convulsive therapy (ECT). Psychiatry Res. 2020; 285:112811. PMC: 7605101. DOI: 10.1016/j.psychres.2020.112811. View

Zhang J, Gao J, Guo G, Li S, Zhan G, Xie Z . Anesthesia and surgery induce delirium-like behavior in susceptible mice: the role of oxidative stress. Am J Transl Res. 2018; 10(8):2435-2444. PMC: 6129548. View

Setters B, Solberg L . Delirium. Prim Care. 2017; 44(3):541-559. DOI: 10.1016/j.pop.2017.04.010. View

Yamanashi T, Malicoat J, Steffen K, Zarei K, Li R, Purnell B . Bispectral EEG (BSEEG) quantifying neuro-inflammation in mice induced by systemic inflammation: A potential mouse model of delirium. J Psychiatr Res. 2020; 133:205-211. DOI: 10.1016/j.jpsychires.2020.12.036. View

Nishizawa Y, Yamanashi T, Saito T, Marra P, Crutchley K, Wahba N . Bispectral EEG (BSEEG) Algorithm Captures High Mortality Risk Among 1,077 Patients: Its Relationship to Delirium Motor Subtype. Am J Geriatr Psychiatry. 2023; 31(9):704-715. DOI: 10.1016/j.jagp.2023.03.002. View

10.

Schreuder L, Eggen B, Biber K, Schoemaker R, Laman J, de Rooij S . Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review. Brain Behav Immun. 2017; 62:362-381. DOI: 10.1016/j.bbi.2017.01.010. View

11.

Liu Y, Jia S, Wang J, Wang D, Zhang X, Liu H . Endocannabinoid signaling regulates post-operative delirium through glutamatergic mediodorsal thalamus-prelimbic prefrontal cortical projection. Front Aging Neurosci. 2022; 14:1036428. PMC: 9752096. DOI: 10.3389/fnagi.2022.1036428. View

12.

Inouye S . Delirium in older persons. N Engl J Med. 2006; 354(11):1157-65. DOI: 10.1056/NEJMra052321. View

13.

Lu Y, Chen L, Ye J, Chen C, Zhou Y, Li K . Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium. Aging (Albany NY). 2020; 12(1):844-865. PMC: 6977661. DOI: 10.18632/aging.102659. View

14.

Hart B . Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988; 12(2):123-37. DOI: 10.1016/s0149-7634(88)80004-6. View

15.

Battista D, Ferrari C, Gage F, Pitossi F . Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci. 2006; 23(1):83-93. DOI: 10.1111/j.1460-9568.2005.04539.x. View

16.

Fong T, Tulebaev S, Inouye S . Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009; 5(4):210-20. PMC: 3065676. DOI: 10.1038/nrneurol.2009.24. View

17.

Ang H, Makpol S, Nasaruddin M, Ahmad N, Tan J, Wan Zaidi W . Lipopolysaccharide-Induced Delirium-like Behaviour in a Rat Model of Chronic Cerebral Hypoperfusion Is Associated with Increased Indoleamine 2,3-Dioxygenase Expression and Endotoxin Tolerance. Int J Mol Sci. 2023; 24(15). PMC: 10418785. DOI: 10.3390/ijms241512248. View

18.

Tang Y, Le W . Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Mol Neurobiol. 2015; 53(2):1181-1194. DOI: 10.1007/s12035-014-9070-5. View

19.

Illendula M, Osuru H, Ferrarese B, Atluri N, Dulko E, Zuo Z . Surgery, Anesthesia and Intensive Care Environment Induce Delirium-Like Behaviors and Impairment of Synaptic Function-Related Gene Expression in Aged Mice. Front Aging Neurosci. 2020; 12:542421. PMC: 7544741. DOI: 10.3389/fnagi.2020.542421. View

20.

Hoogland I, Houbolt C, van Westerloo D, van Gool W, van de Beek D . Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation. 2015; 12:114. PMC: 4470063. DOI: 10.1186/s12974-015-0332-6. View