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

Abstract 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...

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Autores principales: Seth Tigchelaar, Femke Streijger, Sunita Sinha, Stephane Flibotte, Neda Manouchehri, Kitty So, Katelyn Shortt, Elena Okon, Michael A. Rizzuto, Ivana Malenica, Amanda Courtright-Lim, Andrew Eisen, Kendall Van Keuren-Jensen, Corey Nislow, Brian K. Kwon
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:c6dd30671e5d45519ced5dd8ee820ad42021-12-02T12:30:19ZSerum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury10.1038/s41598-017-01299-x2045-2322https://doaj.org/article/c6dd30671e5d45519ced5dd8ee820ad42017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01299-xhttps://doaj.org/toc/2045-2322Abstract 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.Seth TigchelaarFemke StreijgerSunita SinhaStephane FlibotteNeda ManouchehriKitty SoKatelyn ShorttElena OkonMichael A. RizzutoIvana MalenicaAmanda Courtright-LimAndrew EisenKendall Van Keuren-JensenCorey NislowBrian K. KwonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Seth Tigchelaar
Femke Streijger
Sunita Sinha
Stephane Flibotte
Neda Manouchehri
Kitty So
Katelyn Shortt
Elena Okon
Michael A. Rizzuto
Ivana Malenica
Amanda Courtright-Lim
Andrew Eisen
Kendall Van Keuren-Jensen
Corey Nislow
Brian K. Kwon
Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
description Abstract 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.
format article
author Seth Tigchelaar
Femke Streijger
Sunita Sinha
Stephane Flibotte
Neda Manouchehri
Kitty So
Katelyn Shortt
Elena Okon
Michael A. Rizzuto
Ivana Malenica
Amanda Courtright-Lim
Andrew Eisen
Kendall Van Keuren-Jensen
Corey Nislow
Brian K. Kwon
author_facet Seth Tigchelaar
Femke Streijger
Sunita Sinha
Stephane Flibotte
Neda Manouchehri
Kitty So
Katelyn Shortt
Elena Okon
Michael A. Rizzuto
Ivana Malenica
Amanda Courtright-Lim
Andrew Eisen
Kendall Van Keuren-Jensen
Corey Nislow
Brian K. Kwon
author_sort Seth Tigchelaar
title Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
title_short Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
title_full Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
title_fullStr Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
title_full_unstemmed Serum MicroRNAs Reflect Injury Severity in a Large Animal Model of Thoracic Spinal Cord Injury
title_sort serum micrornas reflect injury severity in a large animal model of thoracic spinal cord injury
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/c6dd30671e5d45519ced5dd8ee820ad4
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