Malicoat, J. R. | bioRxiv Science

bioRxiv2024

LPS-induced delirium-like behavior and microglial activation in mice correlate with bispectral electroencephalography (BSEEG)

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 (LPS)-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 LPS-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an LPS-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.

neuroscience↗

bioRxiv2024

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

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.

neuroscience↗