Dataset Information

The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral Z-Scoring.

ABSTRACT: Objective:Patients undergoing major surgeries may experience certain cognitive decline, which is known as postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). We employed integrated behavioral Z-scoring introduced by Guilloux et al. (2011) to investigate the effects of fracture fixation under anesthesia on hippocampus-dependent memory in mice. Methods:ICR mice (12-14 months) underwent stabilized tibial fracture operation under sevoflurane anesthesia. They were subjected to a battery of successive hippocampus-dependent tests following surgery, including open field test (OF), novel object recognition (NOR), fear conditioning test (FC), and Morris water maze (MWM). The integrated behavioral Z-scoring was applied to assess the hippocampus-dependent memory after anesthesia/surgery, and the association between the integrated behavioral Z-scores and hippocampal pro-inflammatory cytokines was explored. Results:Mice after anesthesia/surgery were found to have impaired hippocampus-dependent memory in NOR, FC, and MWM but with different degrees in these aspects as represented by P-value and effect size. The integrated memory Z-scores based on principal parameters of the above three tests can reduced the variability and increase the comprehensiveness of behavioral results. However, we found no statistic associations between hippocampal pro-inflammatory cytokines and the integrated Z-scores, as the elevated cytokines quickly return to normal on postoperative day 3 and/or day 7. Conclusion:The integrated Z-score methodology could facilitate the interpretation of the anesthesia/surgery induced cognitive decline in mice and robustly quantify the behavioral phenotyping of hippocampus-dependent memory.

SUBMITTER: Meng B

PROVIDER: S-EPMC6987045 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral <i>Z</i>-Scoring.

Meng Bo B Li Xiaoyu X Lu Bo B Liu Rongjun R Yuan Hui H Zhai Xiaojie X Qin Jinling J Chen Zhang Z Zheng Jinwei J Chen Junping J

Frontiers in behavioral neuroscience 20200122

<h4>Objective</h4>Patients undergoing major surgeries may experience certain cognitive decline, which is known as postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). We employed integrated behavioral <i>Z-</i>scoring introduced by Guilloux et al. (2011) to investigate the effects of fracture fixation under anesthesia on hippocampus-dependent memory in mice.<h4>Methods</h4>ICR mice (12-14 months) underwent stabilized tibial fracture operation under sevoflurane anesthesia. ...[more]

PMID: 32038186

Similar Datasets

Project description:BackgroundThe impact of anesthesia and surgery on neurocognitive and behavioral development in infants and children remains inadequately understood.ObjectiveTo investigate the impact of early-life exposure to general anesthesia and surgery on cognitive and behavioral development.Methods and materialsChildren aged 0-3 years who underwent general anesthesia and surgical procedures between 2012 and 2015 were included. The cognitive and behavioral development of these children at ages 4-6 years was assessed. Age-, race-, and gender-matched children from the same geographic region, who did not undergo general anesthesia or surgery, served as the control group. The Wechsler Preschool Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to evaluate children's total intelligence quotient (FSIQ) and specific cognitive domains. The Gesell Development Schedules (GSCH) and Child Behavior Checklist (CBCL) were employed to assess behavioral and personality development. Additionally, the study analyzed the effects of various factors including anesthesia drugs, surgery duration, number of surgeries, age, weight, ethnicity, and gender on postoperative neurocognitive and behavioral outcomes.ResultsThe study included 447 children with anesthesia/surgical exposure (AS) and 459 children in the control group. Analysis of cognitive and behavioral development showed a significant difference in the working memory index (WMI) between the AS and control groups (p < 0.05). Exploratory findings indicated that children administered remifentanil exhibited lower developmental quotient (DQ) values, whereas those given fentanyl showed higher (worse) Child Behavior Checklist (CBCL) total scores. Moreover, increased anesthesia/surgical exposures, younger age and lower body weight at exposure, and longer surgery durations were associated with cognitive and behavioral developmental challenges.ConclusionThis study examined the impact of early-life exposure to surgery and anesthesia on postoperative cognitive and behavioral development. Findings indicate that higher frequency of exposure to surgery and anesthesia, younger age, and lower body weight at exposure could negatively influence cognitive and behavioral development. Furthermore, variations in the effects of different anesthetics on behavior and cognition were observed. Caution is advised regarding the use of opioid analgesics such as remifentanil and fentanyl for more rigorous clinical applications.

Project description:WHAT WE ALREADY KNOW ABOUT THIS TOPIC:Cardiac surgery is associated with cognitive decline and postoperative delirium. The relationship between postoperative delirium and cognitive decline after cardiac surgery is unclear WHAT THIS ARTICLE TELLS US THAT IS NEW:The development of postoperative delirium is associated with a greater degree of cognitive decline 1 month after cardiac surgery. The development of postoperative delirium is not a predictor of cognitive decline 1 yr after cardiac surgery. BACKGROUND:Delirium is common after cardiac surgery and has been associated with morbidity, mortality, and cognitive decline. However, there are conflicting reports on the magnitude, trajectory, and domains of cognitive change that might be affected. The authors hypothesized that patients with delirium would experience greater cognitive decline at 1 month and 1 yr after cardiac surgery compared to those without delirium. METHODS:Patients who underwent coronary artery bypass and/or valve surgery with cardiopulmonary bypass were eligible for this cohort study. Delirium was assessed with the Confusion Assessment Method. A neuropsychologic battery was administered before surgery, at 1 month, and at 1 yr later. Linear regression was used to examine the association between delirium and change in composite cognitive Z score from baseline to 1 month (primary outcome). Secondary outcomes were domain-specific changes at 1 month and composite and domain-specific changes at 1 yr. RESULTS:The incidence of delirium in 142 patients was 53.5%. Patients with delirium had greater decline in composite cognitive Z score at 1 month (greater decline by -0.29; 95% CI, -0.54 to -0.05; P = 0.020) and in the domains of visuoconstruction and processing speed. From baseline to 1 yr, there was no difference between delirious and nondelirious patients with respect to change in composite cognitive Z score, although greater decline in processing speed persisted among the delirious patients. CONCLUSIONS:Patients who developed delirium had greater decline in a composite measure of cognition and in visuoconstruction and processing speed domains at 1 month. The differences in cognitive change by delirium were not significant at 1 yr, with the exception of processing speed.

Project description:BackgroundPostoperative cognitive dysfunction (POCD) is a common neurological complication following anesthesia and surgery. Increasing evidence has demonstrated that neuroinflammation caused by systemic inflammatory responses during the perioperative period is a key factor in the occurrence of POCD. In addition, SMAD family member 7 (Smad7) has been confirmed to play vital roles in the pathogenesis and treatment of inflammatory diseases, such as inflammatory bowel disease. However, whether Smad7 participates in the regulatory process of neuroinflammation and apoptosis in the development of POCD is still unknown.MethodsIn this study, a POCD mouse model was constructed by unilateral nephrectomy under anesthesia, and cognitive function was assessed using the fear conditioning test and open field test. The expression of Smad7 at the mRNA and protein levels in the hippocampus 3 days after surgery was examined by qRT-PCR, western blot and immunofluorescence assays. Furthermore, to identify whether the elevation of Smad7 in the hippocampus after unilateral nephrectomy contributes to cognitive impairment, the expression of Smad7 in the hippocampal CA1 region was downregulated by crossing Smad7fl/fl conditional mutant mice and CaMKIIα-Cre line T29-1 transgenic mice or stereotaxic injection of shRNA-Smad7. Inflammation and apoptosis in the hippocampus were assessed by measuring the mRNA levels of typical inflammatory cytokines, including TNF-α, IL-1β, IL-6, CCL2, CXCL1, and CXCL2, and the protein levels of apoptotic proteins, including Bax and Bcl2. In addition, apoptosis in the hippocampus postoperation was investigated by a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining assay. Finally, western blotting was used to explore how Smad7 mediates inflammation and apoptosis postoperation.ResultsThe results unequivocally revealed that elevated Smad7 in the hippocampal CA1 region significantly inhibited TGF-β signal transduction by blocking Smad2/3 phosphorylation, which enhanced neuroinflammation and apoptosis in the hippocampus and further led to learning and memory impairment after surgery.ConclusionsOur results revealed that Smad7 contributes to cognitive impairment after surgery by enhancing neuroinflammation and apoptosis in the hippocampus and might serve as a promising therapeutic target for the treatment of memory impairment after anesthesia surgery.

Dataset Information

The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral Z-Scoring.

Publications

The Investigation of Hippocampus-Dependent Cognitive Decline Induced by Anesthesia/Surgery in Mice Through Integrated Behavioral <i>Z</i>-Scoring.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets