TY - JOUR
T1 - A Targeted Proteomics Analysis of Cerebrospinal Fluid after Acute Human Spinal Cord Injury
AU - Streijger, Femke
AU - Skinnider, Michael A.
AU - Rogalski, Jason C.
AU - Balshaw, Robert
AU - Shannon, Casey P.
AU - Prudova, Anna
AU - Belanger, Lise
AU - Ritchie, Leanna
AU - Tsang, Angela
AU - Christie, Sean
AU - Parent, Stefan
AU - Mac-Thiong, Jean Marc
AU - Bailey, Christopher
AU - Urquhart, Jennifer
AU - Ailon, Tamir
AU - Paquette, Scott
AU - Boyd, Michael
AU - Street, John
AU - Fisher, Charles G.
AU - Dvorak, Marcel F.
AU - Borchers, Christoph H.
AU - Foster, Leonard J.
AU - Kwon, Brian K.
N1 - Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - 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.
AB - 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.
KW - CSF
KW - SCI
KW - biomarkers
KW - injury severity
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85020284745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020284745&partnerID=8YFLogxK
U2 - 10.1089/neu.2016.4879
DO - 10.1089/neu.2016.4879
M3 - Article
C2 - 28276985
AN - SCOPUS:85020284745
SN - 0897-7151
VL - 34
SP - 2054
EP - 2068
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 12
ER -