Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury

医学 脊髓损伤 生物标志物 临床试验 脊髓 小RNA 生物信息学 麻醉 内科学 基因 生物 生物化学 精神科
作者
Seth Tigchelaar,Femke Streijger,Sunita Sinha,Stéphane Flibotte,Neda Manouchehri,Kitty So,Katelyn Shortt,Elena B. Okon,Michael Rizzuto,Ivana Malenica,Amanda Courtright-Lim,Andrew Eisen,Kendall Van Keuren‐Jensen,Corey Nislow,Brian K. Kwon
出处
期刊:Scientific Reports [Springer Nature]
卷期号:7 (1) 被引量:54
标识
DOI:10.1038/s41598-017-01299-x
摘要

Therapeutic development for spinal cord injury is hindered by the difficulty in conducting clinical trials, which to date have relied solely on functional outcome measures for patient enrollment, stratification, and evaluation. Biological biomarkers that accurately classify injury severity and predict neurologic outcome would represent a paradigm shift in the way spinal cord injury clinical trials could be conducted. MicroRNAs have emerged as attractive biomarker candidates due to their stability in biological fluids, their phylogenetic similarities, and their tissue specificity. Here we characterized a porcine model of spinal cord injury using a combined behavioural, histological, and molecular approach. We performed next-generation sequencing on microRNAs in serum samples collected before injury and then at 1, 3, and 5 days post injury. We identified 58, 21, 9, and 7 altered miRNA after severe, moderate, and mild spinal cord injury, and SHAM surgery, respectively. These data were combined with behavioural and histological analysis. Overall miRNA expression at 1 and 3 days post injury strongly correlates with outcome measures at 12 weeks post injury. The data presented here indicate that serum miRNAs are promising candidates as biomarkers for the evaluation of injury severity for spinal cord injury or other forms of traumatic, acute, neurologic injury.
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