GC–MS Based Serum Metabolomic Analysis of Isoflurane-Induced Postoperative Cognitive Dysfunctional Rats: Biomarker Screening and Insight into Possible Pathogenesis

• Published in: Chromatographia Vol. 75; no. 13-14; pp. 799 - 808
• Main Authors: Zhang, Wan, Zhang, Liangxiao, Li, Hongdong, Liang, Yizeng, Hu, Rong, Liang, Nannan, Fan, Wei, Cao, Dongsheng, Yi, Lunzhao, Xia, Jidong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2012; Springer
• Subjects: Analytical Chemistry; Biological and medical sciences; Chemistry; Chemistry and Materials Science; Chromatography; Drug toxicity and drugs side effects treatment; Laboratory Medicine; Medical sciences; Original; Pharmacology. Drug treatments; Pharmacy; Proteomics; Toxicity: nervous system and muscle; Metabolic profiling; Biomarker discovery; Subwindow permutation analysis; Postoperative cognitive dysfunction; Gas chromatography–mass spectrometry; Biological fluid; Metabolomics; Chemical analysis; Cognitive disorder; Rat; Metabolite; Biological marker; Nervous system; Blood; Secondary effect; Halogen Organic compounds; Volatile compound; Postoperative; Coupled method; Rodentia; Gas chromatography-mass spectrometry; Isoflurane; Gas chromatography; Vertebrata; Mammalia; General anesthetic; Animal; Blood serum; Mass spectrometry; Chemometrics; Principal component analysis
• ISSN: 0009-5893; 1612-1112
• DOI: 10.1007/s10337-012-2246-0

Postoperative cognitive dysfunction (POCD) is a subtle cognitive dysfunction, especially memory impairment for weeks or months after surgery. The underlying pathophysiological mechanism of POCD is still unclear. The aim of this study was to exploratively investigate the potential mechanism of POCD by identifying the differences among metabolic profiles of control rats, POCD and no-POCD rats after isoflurane anesthesia based on GC–MS, and subsequently discovering POCD biomarkers. In this paper, a feature-variable selection method, subwindow permutation analysis (SPA), was employed to seek the key metabolites distinguishing POCD from control group, POCD from no-POCD group. Fortunately, two key metabolites, hexadecanoic acid and myo -Inositol, were both screened out for discriminating POCD and control, POCD and no-POCD rats. It suggested that they may reveal the disturbances between POCD and control, POCD and no-POCD rats, which may be the potential biomarkers of POCD. Furthermore, related possible pathogenesis was taken into account on the basis of the relevant literatures and pathway databases. It suggested that POCD was probably related to disturbed hexadecanoic acid metabolism and myo -Inositol metabolism. All the results demonstrated that the proposed metabolic profiling approach and SPA method may be effective for exploring metabolic perturbations and possible biomarkers for POCD.