Identification of Serum Metabolites as Prognostic Biomarkers Following Spinal Cord Injury: A Pilot Study

Abstract

The assessment, management, and prognostication of spinal cord injury (SCI) mainly rely upon observer-based ordinal scales measures. 1H nuclear magnetic resonance (NMR) spectroscopy provides an effective approach for the discovery of objective biomarkers from biofluids. These biomarkers have the potential to aid in understanding recovery following SCI. This proof-of-principle study determined: (a) If temporal changes in blood metabolites reflect the extent of recovery following SCI; (b) whether changes in blood-derived metabolites serve as prognostic indicators of patient outcomes based on the spinal cord independence measure (SCIM); and (c) whether metabolic pathways involved in recovery processes may provide insights into mechanisms that mediate neural damage and repair. Morning blood samples were collected from male complete and incomplete SCI patients (n = 7) following injury and at 6 months post-injury. Multivariate analyses were used to identify changes in serum metabolic profiles and were correlated to clinical outcomes. Specifically, acetyl phosphate, 1,3,7-trimethyluric acid, 1,9-dimethyluric acid, and acetic acid significantly related to SCIM scores. These preliminary findings suggest that specific metabolites may serve as proxy measures of the SCI phenotype and prognostic markers of recovery. Thus, serum metabolite analysis combined with machine learning holds promise in understanding the physiology of SCI and aiding in prognosticating outcomes following injury.

Blood-Derived Metabolic Signatures as Biomarkers of Injury Severity in Traumatic Brain Injury: A Pilot Study

“…Pathway analysis also indicated that pyruvate metabolism was potentially altered, which is in agreement with a parallel study examining blood-derived biomarkers amongst male SCI participants, where it was found that pyruvate metabolism was the most significantly altered pathway [9]. Pyruvate is generated from the metabolism of glucose, and the lactate/pyruvate ratio is a clinically informative measure indicative of cerebral metabolic state [34].…”

“…Another pathway found to be potentially affected post-TBI was alanine, aspartate, and glutamate metabolism. In our parallel study examining blood-derived biomarkers amongst SCI subjects, this pathway also presented as potentially altered, as evidenced by pathway analysis [9]. It is known that the excitatory amino acids aspartate and glutamate are upregulated following insult to the spinal cord [40,41], and this may also be extrapolated to include TBI.…”

“…In an effort to expand the repository for potential biomarkers, our team has shown that metabolites in urine samples collected from athletes with concussion resulted in significantly distinct metabolic profiles at baseline and post-injury [6]. Furthermore, urine and serum sample analysis provided robust metabolic biomarkers for spinal cord injury (SCI) and TBI using 1 H nuclear magnetic resonance (NMR) spectroscopy [7][8][9]. 1 H NMR spectroscopy is especially amenable to detecting metabolic changes in the blood, as it can detect 49 compounds, with 20 of these being unique to NMR [10].…”

Data-driven prediction of spinal cord injury recovery: an exploration of current status and future perspectives

“…8 weeks) after injury. One study used input data from between 3 weeks and 3 months [68] the remaining studies, the specific timing of input data acquisition was either unclear (22 studies) or not reported (9 studies). For outcomes, 21 out of 42 studies with reported time points predicted at up to 1 year post-injury.…”

Unraveling Metabolic Changes following Stroke: Insights from a Urinary Metabolomics Analysis

“…NMR is highly reproducible, non-destructive to the sample, and non-biased, it requires little sample preparation and analysis [ 6 , 9 , 10 ], and it can simultaneously identify metabolites involved in biological processes [ 5 ]; however, NMR is only able to quantify metabolites at micromolar concentrations and requires more sample volume, while mass spectrometry-based metabolomic methods are capable of quantifying at the nanomolar level and require much less sample volume. Previously, NMR spectroscopy has been used in the development of biomarkers for stroke [ 7 ], Alzheimer’s disease [ 11 ], spinal cord injury [ 12 , 13 ], traumatic brain injury [ 14 ], and sport-related concussion [ 15 , 16 ].…”