• Neuroscience · May 2020

    Elevated acute plasma miR-124-3p level relates to evolution of larger cortical lesion area after traumatic brain injury.

    • Niina Vuokila, Shalini Das Gupta, Riina Huusko, Jussi Tohka, Noora Puhakka, and Asla Pitkänen.
    • A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
    • Neuroscience. 2020 May 1; 433: 21-35.

    AbstractMechanisms initiated by traumatic brain injury (TBI), leading to the development of progressive secondary injury are poorly understood. MicroRNAs (miRNAs) have a proposed role in orchestrating the post-injury aftermath as a single miRNA can control the expression of several genes. We hypothesized that the post-injury level of circulating brain-enriched miR-124-3p explains the extent of post-TBI cortical lesion. Three separate cohorts of adult male Sprague-Dawley rats (total n = 57) were injured with lateral fluid-percussion-induced TBI. The miR-124-3p levels were measured in whole blood and/or plasma in cohorts 1 and 2 before TBI as well as at 2 d, 7 d, 2 months or 3 months post-TBI. The third cohort (22/57) was imaged with T2-weighted magnetic resonance imaging (MRI) at 2 months post-TBI to quantify cortical lesion area and perilesional T2-enhancement volume. Our data shows that miR-124-3p levels were elevated at 2 d post-TBI in both blood (FC 4.63, p < 0.01) and plasma (FC 1.39, p < 0.05) as compared to controls. Receiver operating curve (ROC) analysis indicated that plasma miR-124-3p level of 34 copies/µl or higher differentiated TBI animals from controls [area under curve (AUC) 0.815, p < 0.05]. The data was validated in the third cohort (FC 1.68, p < 0.05). T2-weighted MRI revealed inter-animal differences in cortical lesion area. Linear regression analysis revealed that higher the plasma miR-124-3p level at 2 d post-TBI, larger the lesion area at chronic time point (R2 = 0.327, p < 0.01). Our findings indicate that the extent of lateral fluid-percussion injury-induced chronic cortical pathology associated with the acutely elevated plasma miR-124-3p level.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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