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Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

ABSTRACT: Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.

SUBMITTER: Cheon SY

PROVIDER: S-EPMC8052461 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

Cheon So Yeong SY Koo Bon-Nyeo BN Kim So Yeon SY Kam Eun Hee EH Nam Junhyun J Kim Eun Jung EJ

Scientific reports 20210416 1

Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatr ...[more]

PMID: 33863952

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Project description:BackgroundPatients in the intensive care unit (ICU) are known to be at increased risk of developing delirium, but the risk of subsequent neuropsychiatric disorders is unclear. We therefore sought to examine the association between the presence of delirium in the ICU and incident neuropsychiatric disorders (including depressive, anxiety, trauma-and-stressor-related, and neurocognitive disorders) post-ICU stay among adult medical-surgical ICU patients.MethodsRetrospective cohort study utilizing clinical and administrative data from both inpatient and outpatient healthcare visits to identify the ICU cohort and diagnostic information 5 years prior to and 1 year post-ICU stay. Patients ≥ 18 years of age admitted to one of 14 medical-surgical ICUs across Alberta, Canada, January 1, 2014-June 30, 2016, and survived to hospital discharge were included. The main outcome of interest was a new diagnosis of any neuropsychiatric disorder 1 year post-ICU stay. The exposure variable was delirium during the ICU stay identified through any positive delirium screen by the Intensive Care Unit Delirium Screening Checklist (ICDSC) during the ICU stay.ResultsOf 16,005 unique patients with at least one ICU admission, 4033 patients were included in the study of which 1792 (44%) experienced delirium during their ICU stay. The overall cumulative incidence of any neuropsychiatric disorder during the subsequent year was 19.7% for ICU patients. After adjusting for hospital characteristics using log-binomial regression, patients with delirium during the ICU stay had a risk ratio (RR) of 1.14 (95% confidence interval [CI] 0.98-1.33) of developing any neuropsychiatric disorder within 1 year post-ICU compared to those who did not experience delirium. Delirium was significantly associated with neurocognitive disorders (RR 1.59, 95% CI 1.08-2.35), but not depressive disorders (RR 1.16, 95% CI 0.92-1.45), anxiety (RR 1.16, 95% CI 0.92-1.47), and trauma-and-stressor-related (RR 0.82, 95% CI 0.53-1.28) disorders.ConclusionsThe diagnosis of new onset of neurocognitive disorders is associated with ICU-acquired delirium. In this study, significant associations were not observed for depressive, anxiety, and trauma-and-stressor-related disorders.

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Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

Publications

Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

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