title: A Targeted Proteomics Analysis of Cerebrospinal Fluid after Acute Human Spinal Cord Injury.
abstract: Efforts to validate novel therapies in acute clinical trials for spinal cord injury (SCI) are impeded by the lack of objective quantitative measures that reflect injury severity and accurately predict neurological recovery. Therefore, a strong rationale exists for establishing neurochemical biomarkers that objectively quantify injury severity and predict outcome. Here, we conducted a targeted proteomics analysis of cerebrospinal fluid (CSF) samples derived from 29 acute SCI patients (American Spinal Injury Association Impairment Scale [AIS] A, B, or C) acquired at 24, 48, and 72 h post-injury. From a total of 165 proteins, we identified 27 potential biomarkers of injury severity (baseline AIS A, B, or C), with triosephosphate isomerase having the strongest relationship to AIS grade. The majority of affected proteins (24 of 27) were more abundant in samples from AIS A patients than in those from AIS C patients, suggesting that for the most part, these proteins are released into the CSF more readily with more severe trauma to the spinal cord. We then analyzed the relationship between CSF protein abundance and neurological recovery. For AIS grade improvement over 6 months, we identified 34 proteins that were associated with AIS grade conversion (p < 0.05); however, these associations were not statistically significant after adjusting for multiple comparisons. For total motor score (TMS) recovery over 6 months, after adjusting for baseline neurological injury level, we identified 46 proteins with a statistically significant association with TMS recovery. Twenty-two of these proteins were among the 27 proteins that were related to baseline AIS grade, consistent with the notion that protein markers that reflect a more severe injury also appropriately predict a poorer recovery of motor function. In summary, this study provides a description of the CSF proteome changes that occur after acute human SCI, and reveals a number of protein candidates for further validation as potential biomarkers of injury severity.
authors.affiliation: 1 International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Femke
authors.initials: F
authors.lastname: Streijger
authors.affiliation: 2 Department of Biochemistry & Molecular Biology and Michael Smith Laboratories, University of British Columbia , Vancouver, British Columbia, Canada .|3 Genome Sciences & Technologies Graduate Program, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinnider
authors.affiliation: 2 Department of Biochemistry & Molecular Biology and Michael Smith Laboratories, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Jason C
authors.initials: JC
authors.lastname: Rogalski
authors.affiliation: 4 BC Center for Disease Control , Vancouver, British Columbia, Canada .|5 PROOF Centre of Excellence , Vancouver, British Columbia, Canada .
authors.forename: Robert
authors.initials: R
authors.lastname: Balshaw
authors.affiliation: 5 PROOF Centre of Excellence , Vancouver, British Columbia, Canada .
authors.forename: Casey P
authors.initials: CP
authors.lastname: Shannon
authors.affiliation: 2 Department of Biochemistry & Molecular Biology and Michael Smith Laboratories, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Anna
authors.initials: A
authors.lastname: Prudova
authors.affiliation: 6 Vancouver Spine Program, Vancouver, British Columbia, Canada .
authors.forename: Lise
authors.initials: L
authors.lastname: Belanger
authors.affiliation: 6 Vancouver Spine Program, Vancouver, British Columbia, Canada .
authors.forename: Leanna
authors.initials: L
authors.lastname: Ritchie
authors.affiliation: 6 Vancouver Spine Program, Vancouver, British Columbia, Canada .
authors.forename: Angela
authors.initials: A
authors.lastname: Tsang
authors.affiliation: 7 Division of Neurosurgery, Dalhousie University , Halifax Infirmary Halifax, Halifax, Nova Scotia, Canada .
authors.forename: Sean
authors.initials: S
authors.lastname: Christie
authors.affiliation: 8 Department of Surgery, Hôpital du Sacré-Coeur de Montréal, Université de Montréal , Montréal, Quebec, Canada .|9 Chu Sainte-Justine, Department of Surgery, Université de Montréal , Montréal, Quebec, Canada .
authors.forename: Stefan
authors.initials: S
authors.lastname: Parent
authors.affiliation: 8 Department of Surgery, Hôpital du Sacré-Coeur de Montréal, Université de Montréal , Montréal, Quebec, Canada .|9 Chu Sainte-Justine, Department of Surgery, Université de Montréal , Montréal, Quebec, Canada .
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Mac-Thiong
authors.affiliation: 10 Division of Orthopaedic Surgery, London Health Sciences Centre, University of Western Ontario , London, Ontario, Canada .
authors.forename: Christopher
authors.initials: C
authors.lastname: Bailey
authors.affiliation: 10 Division of Orthopaedic Surgery, London Health Sciences Centre, University of Western Ontario , London, Ontario, Canada .
authors.forename: Jennifer
authors.initials: J
authors.lastname: Urquhart
authors.affiliation: 11 Vancouver Spine Surgery Institute, Division of Neurosurgery, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Tamir
authors.initials: T
authors.lastname: Ailon
authors.affiliation: 11 Vancouver Spine Surgery Institute, Division of Neurosurgery, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Scott
authors.initials: S
authors.lastname: Paquette
authors.affiliation: 11 Vancouver Spine Surgery Institute, Division of Neurosurgery, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.affiliation: 12 Department of Orthopaedics, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: John
authors.initials: J
authors.lastname: Street
authors.affiliation: 12 Department of Orthopaedics, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Charles G
authors.initials: CG
authors.lastname: Fisher
authors.affiliation: 12 Department of Orthopaedics, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Dvorak
authors.affiliation: 13 UVic-Genome BC Proteomics Centre , Victoria, British Columbia, Canada .
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.affiliation: 2 Department of Biochemistry & Molecular Biology and Michael Smith Laboratories, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.affiliation: 1 International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, University of British Columbia , Vancouver, British Columbia, Canada .|12 Department of Orthopaedics, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers
keywords: CSF; SCI; biomarkers; injury severity; proteomics