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

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Date
2020
Author(s)
Vuokila, Niina
Gupta, Shalini Das
Huusko, Riina
Tohka, Jussi
Puhakka, Noora
Pitkänen, Asla
Unique identifier
10.1016/j.neuroscience.2020.02.045
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Citation
Vuokila, Niina. Gupta, Shalini Das. Huusko, Riina. Tohka, Jussi. Puhakka, Noora. Pitkänen, Asla. (2020). Elevated acute plasma miR-124-3p level relates to evolution of larger cortical lesion area after traumatic brain injury.  Neuroscience, 433, 21-35. 10.1016/j.neuroscience.2020.02.045.
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© IBRO
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CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
Abstract

Mechanisms 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.

Subjects
microRNA   miR-124-3p   plasma   prognostic biomarker   receiver operating characteristic curve   traumatic brain injury   
URI
https://erepo.uef.fi/handle/123456789/8126
Link to the original item
http://dx.doi.org/10.1016/j.neuroscience.2020.02.045
Publisher
Elsevier BV
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  • Terveystieteiden tiedekunta [1336]
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