Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous syste
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METHOD PAPER
Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system–related pathological processes Simone Bohnert 1 & Christoph Reinert 1 & Stefanie Trella 1 & Werner Schmitz 2 & Benjamin Ondruschka 3 & Michael Bohnert 1 Received: 30 August 2020 / Accepted: 5 November 2020 # The Author(s) 2020
Abstract In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples. Keywords CSF . Cerebrospinal fluid . Forensic neuropathology . Forensic neurotraumatology . Biomarker . Metabolomics
Introduction In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in diagnostic medicine, which is applied both in routine diagnostic tests as well as in clinical studies. In the clinical laboratory, analysis of the metabolome is used especially for identifying biomarkers for predisposition, diagnosis, or treatment of various diseases. By investigating metabolic changes associated with a special disease, scientists hope to gain a better Benjamin Ondruschka and Michael Bohnert contributed equally to this work. * Simone Bohnert [email protected] 1
Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078 Wuerzburg, Germany
2
Institute of Biochemistry and Molecular Biology I, Biozentrum - Am Hubland, 97074 Wuerzburg, Germany
3
Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Germany
understanding of the pathophysiology and individual risk assessment of complex illnesses such as diabetes mellitus, coronary heart disease, or cancer [1–5]. Metabolites or “small molecules” are responsible for cellular signal transduction and energy balance; they reflect the biochemical status, i.e., the molecular fingerprint of an organism prior to its phenotypical presentation (see Fig. 1). With t
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