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J Neurotrauma. 2017 Jun 15;34(12):2054-2068. doi: 10.1089/neu.2016.4879. Epub 2017 Apr 7.

A Targeted Proteomics Analysis of Cerebrospinal Fluid after Acute Human Spinal Cord Injury.

Author information

1
1 International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, University of British Columbia , Vancouver, British Columbia, Canada .
2
2 Department of Biochemistry & Molecular Biology and Michael Smith Laboratories, University of British Columbia , Vancouver, British Columbia, Canada .
3
3 Genome Sciences & Technologies Graduate Program, University of British Columbia , Vancouver, British Columbia, Canada .
4
4 BC Center for Disease Control , Vancouver, British Columbia, Canada .
5
5 PROOF Centre of Excellence , Vancouver, British Columbia, Canada .
6
6 Vancouver Spine Program, Vancouver, British Columbia, Canada .
7
7 Division of Neurosurgery, Dalhousie University , Halifax Infirmary Halifax, Halifax, Nova Scotia, Canada .
8
8 Department of Surgery, Hôpital du Sacré-Coeur de Montréal, Université de Montréal , Montréal, Quebec, Canada .
9
9 Chu Sainte-Justine, Department of Surgery, Université de Montréal , Montréal, Quebec, Canada .
10
10 Division of Orthopaedic Surgery, London Health Sciences Centre, University of Western Ontario , London, Ontario, Canada .
11
11 Vancouver Spine Surgery Institute, Division of Neurosurgery, University of British Columbia , Vancouver, British Columbia, Canada .
12
12 Department of Orthopaedics, University of British Columbia , Vancouver, British Columbia, Canada .
13
13 UVic-Genome BC Proteomics Centre , Victoria, British Columbia, Canada .

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.

KEYWORDS:

CSF; SCI; biomarkers; injury severity; proteomics

PMID:
28276985
DOI:
10.1089/neu.2016.4879
[Indexed for MEDLINE]

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