Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to...

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Main Authors: Elani A. Bykowski, Jamie N. Petersson, Sean Dukelow, Chester Ho, Chantel T. Debert, Tony Montina, Gerlinde A.S. Metz
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:IBRO Neuroscience Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667242121000154
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author Elani A. Bykowski
Jamie N. Petersson
Sean Dukelow
Chester Ho
Chantel T. Debert
Tony Montina
Gerlinde A.S. Metz
author_facet Elani A. Bykowski
Jamie N. Petersson
Sean Dukelow
Chester Ho
Chantel T. Debert
Tony Montina
Gerlinde A.S. Metz
author_sort Elani A. Bykowski
collection DOAJ
description Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p < 0.01), 3-hydroxymandelic acid (R= -0.85, p < 0.001), L-valine (R = 0.90, p < 0.001; R = -0.64, p < 0.05), and N-methylhydantoin (R = -0.90, p < 0.001). The most affected pathway was purine metabolism. These findings indicate that urinary metabolites reflect SCI lesion severity and recovery and provide potentially prognostic biomarkers of SCI outcome in precision medicine approaches.
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spelling doaj.art-5f3a1558c6f34383b6fb503a76b7aa7c2022-12-21T20:37:59ZengElsevierIBRO Neuroscience Reports2667-24212021-06-0110178185Urinary biomarkers indicative of recovery from spinal cord injury: A pilot studyElani A. Bykowski0Jamie N. Petersson1Sean Dukelow2Chester Ho3Chantel T. Debert4Tony Montina5Gerlinde A.S. Metz6Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada; Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta, CanadaCanadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada; Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta, Canada; Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, CanadaDivision of Physical Medicine and Rehabilitation, University of Alberta, Edmonton, Alberta, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Correspondence to: Department of Clinical Neurosciences, University of Calgary, 1403 29th St., Calgary, Alberta T2N 2T9, Canada.Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta, Canada; Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada; Correspondence to: Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, Alberta T1K 3M4, Canada.Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada; Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta, Canada; Correspondence to: Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, 4401 University Drive, Alberta T1K 3M4, Canada.Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p < 0.01), 3-hydroxymandelic acid (R= -0.85, p < 0.001), L-valine (R = 0.90, p < 0.001; R = -0.64, p < 0.05), and N-methylhydantoin (R = -0.90, p < 0.001). The most affected pathway was purine metabolism. These findings indicate that urinary metabolites reflect SCI lesion severity and recovery and provide potentially prognostic biomarkers of SCI outcome in precision medicine approaches.http://www.sciencedirect.com/science/article/pii/S2667242121000154Metabolomics1H NMR spectroscopyUrineSpinal cord injuryBiomarkersNeurorehabilitation
spellingShingle Elani A. Bykowski
Jamie N. Petersson
Sean Dukelow
Chester Ho
Chantel T. Debert
Tony Montina
Gerlinde A.S. Metz
Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
IBRO Neuroscience Reports
Metabolomics
1H NMR spectroscopy
Urine
Spinal cord injury
Biomarkers
Neurorehabilitation
title Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
title_full Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
title_fullStr Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
title_full_unstemmed Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
title_short Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study
title_sort urinary biomarkers indicative of recovery from spinal cord injury a pilot study
topic Metabolomics
1H NMR spectroscopy
Urine
Spinal cord injury
Biomarkers
Neurorehabilitation
url http://www.sciencedirect.com/science/article/pii/S2667242121000154
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