Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study

Background: Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective: Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if u...

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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 2021-12-01
Series:IBRO Neuroscience Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667242121000452
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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 Background: Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective: Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. Methods: Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. Results: Lower levels of homovanillate (R = −0.74, p ≤ 0.001), L-methionine (R = −0.78, p < 0.001), and thymine (R = −0.85, p < 0.001) negatively correlated to injury severity. Pathway analysis revealed purine metabolism to be a primary pathway (p < 0.01) impacted by TBI. Conclusion: This study provides pilot data to support the use of urinary metabolites in clinical practice to better interpret biochemical changes underlying TBI severity and recovery. The discovery of urinary metabolites as biomarkers may assist in objective and rapid identification of TBI severity and prognosis. Thus, 1H NMR metabolomics has the potential to facilitate the adaptation of treatment programs that are personalized to the patient’s needs.
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spelling doaj.art-b7505d2e8e064827bd94284b9ff9d0872022-12-21T18:03:44ZengElsevierIBRO Neuroscience Reports2667-24212021-12-0111200206Urinary metabolomic signatures as indicators of injury severity following traumatic brain 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 Neuroscience, University of Calgary, 2500 University Drive NW, Calgary T2N 1N4, Alberta, 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, The University of Lethbridge, 4401 University Drive W, Lethbridge T1K 3M4, Alberta, 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: Department of Neuroscience, The University of Lethbridge, 4401 University Drive W, Lethbridge T1K 3M4, Alberta, Canada.Background: Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). Objective: Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. Methods: Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. Results: Lower levels of homovanillate (R = −0.74, p ≤ 0.001), L-methionine (R = −0.78, p < 0.001), and thymine (R = −0.85, p < 0.001) negatively correlated to injury severity. Pathway analysis revealed purine metabolism to be a primary pathway (p < 0.01) impacted by TBI. Conclusion: This study provides pilot data to support the use of urinary metabolites in clinical practice to better interpret biochemical changes underlying TBI severity and recovery. The discovery of urinary metabolites as biomarkers may assist in objective and rapid identification of TBI severity and prognosis. Thus, 1H NMR metabolomics has the potential to facilitate the adaptation of treatment programs that are personalized to the patient’s needs.http://www.sciencedirect.com/science/article/pii/S2667242121000452Traumatic brain injuryConcussionMetabolomicsMetabolic biomarkersNMR spectroscopyRehabilitation
spellingShingle Elani A. Bykowski
Jamie N. Petersson
Sean Dukelow
Chester Ho
Chantel T. Debert
Tony Montina
Gerlinde A.S. Metz
Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
IBRO Neuroscience Reports
Traumatic brain injury
Concussion
Metabolomics
Metabolic biomarkers
NMR spectroscopy
Rehabilitation
title Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
title_full Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
title_fullStr Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
title_full_unstemmed Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
title_short Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study
title_sort urinary metabolomic signatures as indicators of injury severity following traumatic brain injury a pilot study
topic Traumatic brain injury
Concussion
Metabolomics
Metabolic biomarkers
NMR spectroscopy
Rehabilitation
url http://www.sciencedirect.com/science/article/pii/S2667242121000452
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