Citation

Tigchelaar S, Gupta R, Shannon CP, Streijger F, Sinha S, Flibotte S, Rizzuto M, Street J, Paquette SJ, Ailon T, Charest-Morin R, Dea N, Fisher CG, Dvorak MF, Dhall SS, Mac-Thiong JM, Parent S, Bailey C, Christie S, van Keuren-Jensen K, Nislow C, Kwon BK. J. Neurotrauma 2019; 36(15): 2358-2371.

Affiliation

University of British Columbia, International Collaboration on Repair Discoveries (ICORD), Vancouver, British Columbia, Canada ; brian.kwon@ubc.ca.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.6256

PMID

30827169

Abstract

Spinal cord injury (SCI) is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment following SCI is measured and classified by a widely accepted standard neurologic examination. However, in the very acute stages post-injury, this examination is extremely challenging (and often impossible) to conduct, and has modest prognostic value in terms of neurologic recovery. The lack of objective tools to classify injury severity and predict outcome is a barrier for clinical trials and thwarts development of therapies for SCI. Biological markers (biomarkers) represent a promising, complementary approach to these challenges as they represent an unbiased approach to classify injury severity and predict neurologic outcome. Identification of a suitable panel of molecular biomarkers would comprise a fundamental shift in how acute SCI patients are evaluated, stratified, and treated in clinical trials. MicroRNA are attractive biomarker candidates in neurological disorders for several reasons, including their stability in biological fluids, their conservation between humans and model mammals, and their tissue specificity. In this study, we used next-generation sequencing to identify microRNA associated with injury severity within the cerebrospinal fluid (CSF) and serum of human acute SCI patients. CSF and serum samples were obtained 1-5 days post injury from 39 acute SCI patients (24 AIS A, 8 AIS B, 7 AIS C) and from 5 non-SCI controls. We identified a severity-dependent pattern of change in microRNA expression in CSF and identified a set of microRNA that are diagnostic of baseline AIS classification and prognostic of neurologic outcome 6 months post injury. The data presented here provides a comprehensive description of the CSF and serum microRNA expression changes that occur after acute human SCI. This data set reveals microRNA candidates that warrant further evaluation as biomarkers of injury severity after SCI, and as key regulators in other neurological disorders.

Language: en

Keywords

BIOMARKERS; GENOMICS; HUMAN STUDIES; TRAUMATIC SPINAL CORD INJURY