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
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Acknowledgements
This work is dedicated to the memory of our late coworkers Dra. Sandra Porcayo-Liborio and Dr. Rolando Antonio Arguedas Camacho. MEGA gratefully acknowledges CONACYT for the PhD scholarship 295848. This study was developed at LURMN at IQ-UNAM, which is funded by CONACYT—Mexico (Project 0224747), and UNAM. The authors thank for the sample collection to the residents of INNyN Gonzalo Flores Chagolla, Francisco Bejarano Rodríguez, Emma Ortiz Islas, Elizabeth Mendoza Portillo, Fernando Jose Roosemberg Ordonez and Julissa Abreu Ramirez.
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NEE and MLLA conceived the research. SPL, CMRA and JCP selected the subjects, supervised the patient’s care and the sample collection. MEGA and NEE design and perform NMR analysis. MEGA, NEE and ERSM perform chemometric analysis. MEGA and NEE wrote the manuscript. All authors contributed with the data interpretation, read and approved the final manuscript.
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All procedures performed directly from individuals were according to the ethical standards of the Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (Approval Number: 68/17 and 60/18) and performed in accordance with the 1964 Helsinki declaration and its later amendments.
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García-Aguilera, M.E., de San Miguel, E.R., Cruz-Pérez, J. et al. NMR-based metabolomics of human cerebrospinal fluid identifies signature of brain death. Metabolomics 17, 40 (2021). https://doi.org/10.1007/s11306-021-01794-3
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DOI: https://doi.org/10.1007/s11306-021-01794-3