Sleep Fragmentation, Electroencephalographic Slowing, and Circadian Disarray in a Mouse Model for Intensive Care Unit Delirium

Dulko, Elzbieta; Jedrusiak, Michal; Osuru, Hari P.; Atluri, Navya; Illendula, Meghana; Davis, Eric M.; Beenhakker, Mark P.; Lunardi, Nadia

doi:10.1213/ane.0000000000006524

Cited by 3 publications

References 40 publications

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The Bispectral Electroencephalography Method Quantifies Postoperative Delirium-Like States in Young and Aged Male Mice After Head-Mount Implantation Surgery

Nishiguchi,

Shibata,

Yamanishi

et al. 2024

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences

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Delirium, a syndrome characterized by an acute change in attention, awareness, and cognition, is commonly observed in older adults, although there are few quantitative monitoring methods in the clinical setting. We developed a bispectral electroencephalography (BSEEG) method capable of detecting delirium and can quantify the severity of delirium using a novel algorithm. Pre-clinical application of this novel BSEEG method can capture a delirium-like state in mice following LPS administration. However, its application to postoperative delirium (POD) has not yet been validated in animal experiments. This study aimed to create a POD model in mice with the BSEEG method by monitoring BSEEG scores following EEG head-mount implantation surgery and throughout the recovery. We compared the BSEEG scores of C57BL/6J young (2-3 months old) with aged (18-19 months old) male mice for quantitative evaluation of POD-like states. Postoperatively, both groups displayed increased BSEEG scores and a loss of regular diurnal changes in BSEEG scores. In young mice, BSEEG scores and regular diurnal changes recovered relatively quickly to baseline by postoperative day 3. Conversely, aged mice exhibited prolonged increases in postoperative BSEEG scores and it reached steady states only after postoperative day 8. This study suggests that the BSEEG method can be utilized as a quantitative measure of POD and assess the effect of aging on recovery from POD in the pre-clinical model.

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The Bispectral Electroencephalography Method Quantifies Postoperative Delirium-Like States in Young and Aged Male Mice After Head-Mount Implantation Surgery

Nishiguchi,

Shibata,

Yamanishi

et al. 2024

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences

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Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption

Atluri,

Dulko,

Jedrusiak

et al. 2023

Anesthesiology

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Background Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing REM sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study we hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane -exposed and REM sleep-deprived animals is largely similar. Methods Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation or control conditions. Conventional c-Fos immunohistochemistry and genetically-tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. Results REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs 124.2 ± 27.8 min, P=0.003), and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus (SLD), a region active during REM sleep (176.0 ± 36.6 cells vs 58.8 ± 8.7, P=0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray (vlPAG), a region that is inactive during REM sleep (34.8 ± 5.3 cells vs 136.2 ± 19.6, P=0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals, relative to controls (SLD: 85.0 ± 15.5 cells vs 23.0 ± 1.2, P=0.004; vlPAG: 652.8 ± 71.7 cells vs 889.3 ± 66.8, P=0.042). Conclusions In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.

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The bispectral EEG (BSEEG) method quantifies post-operative delirium-like states in young and aged mice after head mount implantation surgery

Nishiguchi,

Shibata,

Yamanishi

et al. 2024

Preprint

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Delirium, a syndrome characterized by an acute change in attention, awareness, and cognition, is commonly observed in older adults and has multiple potential triggers, including illness, drug, trauma, and surgery. There are few quantitative monitoring methods in clinical settings. We developed the bispectral electroencephalography (BSEEG) method in clinical research that can detect the presence of and quantify the severity of delirium using a novel algorithm. In the pre-clinical model, we reported that the BSEEG method can capture a delirium-like state in mice following LPS administration. However, its application to post-operative delirium (POD) has not yet been validated in animal experiments. Therefore, this study aimed to create a POD model mouse with the BSEEG method by monitoring BSEEG scores after EEG head-mount implantation surgery throughout the recovery phase. We compared the BSEEG scores of C57BL/6J young (2-3 months old) with aged (18-19 months old) mice for quantitative evaluation of the delirium-like state after the surgery. Postoperatively, both groups showed increased BSEEG scores and a loss of regular diurnal changes in BSEEG scores every daytime and night. In young mice, BSEEG scores and regular diurnal changes recovered relatively quickly to baseline by around postoperative day 3. On the other hand, aged mice had prolonged increases in postoperative BSEEG scores and it reached steady state only after around postoperative day 8. This study suggests the BSEEG method can be utilized to quantitatively evaluate POD and also assess the effect of aging on recovery from POD in pre-clinical model.

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Sleep Fragmentation, Electroencephalographic Slowing, and Circadian Disarray in a Mouse Model for Intensive Care Unit Delirium

Cited by 3 publications

References 40 publications

The Bispectral Electroencephalography Method Quantifies Postoperative Delirium-Like States in Young and Aged Male Mice After Head-Mount Implantation Surgery

The Bispectral Electroencephalography Method Quantifies Postoperative Delirium-Like States in Young and Aged Male Mice After Head-Mount Implantation Surgery

Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption

The bispectral EEG (BSEEG) method quantifies post-operative delirium-like states in young and aged mice after head mount implantation surgery

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