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A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Low blood S-methyl-5-thioadenosine is associated with postoperative delayed neurocognitive recovery
Lei Zhang1,2, Haoli Mao3, Ren Zhou4
1Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. weiymzhl@126.com.
Abstract:
Elderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.
Insights
Surgery and anesthesia can cause cognitive decline in elderly patients. Lower levels of S-methyl-5-thioadenosine (MTA) may predict this risk, offering a potential biomarker for delayed neurocognitive recovery (dNCR).
Area of Science:
- Neuroscience
- Metabolomics
- Geriatrics
Background:
- Elderly individuals experience metabolite alterations linked to postoperative cognitive impairment.
- The relationship between specific metabolites and delayed neurocognitive recovery (dNCR) after surgery and anesthesia is not well understood.
Purpose of the Study:
- To investigate the association between S-methyl-5-thioadenosine (MTA) and dNCR in elderly patients.
- To identify blood metabolites as potential biomarkers for dNCR following anesthesia and surgery.
Main Methods:
- Widely targeted metabolomics was used to analyze preoperative and postoperative plasma samples from mice and human patients.
- MTA levels and MTA phosphorylase activity were assessed in mouse brains.
- Cognitive function and inflammation were evaluated in mice following MTA administration.
Main Results:
- Anesthesia/surgery decreased MTA levels and activated MTA phosphorylase in mouse brains.
- Preoperative MTA administration in mice prevented inflammation and cognitive decline.
- Patients who developed dNCR had lower preoperative serum MTA levels.
- Both low preoperative and postoperative MTA levels correlated with an increased risk of dNCR.
Conclusions:
- Anesthesia and surgery may induce cognitive decline via alterations in methionine synthesis pathways.
- S-methyl-5-thioadenosine (MTA) shows potential as a perioperative biomarker for predicting dNCR.
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