Elevated Acute Plasma miR-124-3p Level Relates to Evolution of Larger Cortical Lesion Area after Traumatic Brain Injury. (1st May 2020)

• Record Type: Journal Article
• Authors: Vuokila, Niina; Das Gupta, Shalini; Huusko, Riina; Tohka, Jussi; Puhakka, Noora; Pitkänen, Asla
• Is Part Of: Neuroscience. Volume 433(2020)
• Page Start: 21
• Page End: 35
• Publication Date: 2020-05-01
• Subjects: Ainfl area of T2 enhancement -- AIP agranular insular cortex, posterior area -- Au1 primary auditory cortex -- AUC area under curve -- AuD secondary auditory cortex, dorsal area -- AuV secondary auditory cortex, ventral area -- BL baseline -- Ct cycle threshold -- CXcontra volume of contralateral cortex -- CXipsi volume of ipsilateral cortex -- d days -- ddPCR droplet digital polymerase chain reaction -- DI dysgranular insular cortex -- Ect ectorhinal cortex -- FPI fluid percussion injury -- GI granular insular cortex -- Hc hippocampus -- LPtA lateral parietal association cortex -- mo months -- MRI magnetic resonance imaging -- NISSL Nissl staining -- PRh perirhinal cortex -- PtPD parietal cortex, posterior area, dorsal part -- PtPR parietal cortex, posterior area, rostral part -- rf rhinal fissure -- RT-qPCR reverse transcriptase quantitative polymerase chain reaction -- S sham-operated control -- S1 primary somatosensory cortex -- S1BF primary somatosensory cortex, barrel field -- S1ULp primary somatosensory cortex, upper lip region -- S2 secondary somatosensory cortex -- sham sham-operated control rat -- T TBI-induced animal -- TBI traumatic brain injury -- TeA V1 primary visual cortex -- Tha thalamus -- V lateral ventricle -- VIF variance inflation factor, V1, primary visual cortex -- V1B primary visual cortex, binocular area -- V1M primary visual cortex, monocular area -- V2L secondary visual cortex, lateral area; microRNA -- miR-124-3p -- plasma -- prognostic biomarker -- receiver operating characteristic curve -- traumatic brain injury; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.02.045
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Evolution of cortical pathology after lateral fluid-percussion injury is variable. Characteristics of primary impact do not explain variability in the evolution of cortical pathology. Plasma miR-124-3p level presents a prognostic biomarker for the evolution of cortical pathology. 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 ( R 2 = 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.