NMR-based metabolomics of human cerebrospinal fluid identifies signature of brain death

Abstract

Introduction Brain death (BD) is the irreversible cessation of all functions of the entire brain, including the brainstem. Cerebrospinal fluid (CSF) is a biological liquid that circulates in brain and spine. Metabolomics is able to reveal the response of biological systems to diverse factors in a specific moment or condition. Therefore, the study of this neurological condition through metabolic profiling using high resolution Nuclear Magnetic Resonance (NMR) spectroscopy is important for understanding biochemical events. Objectives The aim of the current study is to identify the metabolomics signature of BD using ¹H-NMR spectroscopy in human CSF. Methods ¹H-NMR spectroscopy has been employed for metabolomic untargeted analysis in 46 CSF samples: 22 control and 24 with BD. Spectral data were further subjected to multivariate analysis. Results Statistically significant multivariate models separated subject’s samples with BD from controls and revealed twenty one discriminatory metabolites. The statistical analysis of control and BD subjects using Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) model resulted in R²X of 0.733 and Q² of 0.635. An elevation in the concentration of statistically discriminant metabolites in BD was observed. Conclusion This study identifies a metabolic signature associated with BD and the most relevant enriched selected metabolic pathways. Graphic Abstract