Vuokila Niina, Das Gupta Shalini, Huusko Riina, Tohka Jussi, Puhakka Noora, Pitkänen Asla
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Natural Resources Institute Finland (Luke), PO Box 413, FI-90014 Oulu, Finland.
Neuroscience. 2020 May 1;433:21-35. doi: 10.1016/j.neuroscience.2020.02.045. Epub 2020 Mar 4.
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 = 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.
创伤性脑损伤（TBI）引发的导致进行性继发性损伤发展的机制目前仍知之甚少。微小RNA（miRNA）在协调损伤后的后果中可能发挥作用，因为单个miRNA可以控制多个基因的表达。我们假设循环中脑富集的miR-124-3p的损伤后水平可以解释TBI后皮质损伤的程度。将三组成年雄性Sprague-Dawley大鼠（共n = 57只）通过侧方液压冲击诱导TBI。在第1组和第2组中，在TBI前以及TBI后2天、7天、2个月或3个月时测量全血和/或血浆中的miR-124-3p水平。第三组（22/57）在TBI后2个月时用T2加权磁共振成像（MRI）进行成像，以量化皮质损伤面积和损伤周围T2增强体积。我们的数据表明，与对照组相比，TBI后2天时血液（FC 4.63，p < 0.01）和血浆（FC 1.39，p < 0.05）中的miR-124-3p水平均升高。受试者操作特征曲线（ROC）分析表明，血浆miR-124-3p水平为34拷贝/µl或更高可区分TBI动物与对照组[曲线下面积（AUC）0.815，p < 0.05]。该数据在第三组中得到验证（FC 1.68，p < 0.05）。T2加权MRI显示动物之间皮质损伤面积存在差异。线性回归分析表明，TBI后2天时血浆miR-124-3p水平越高，慢性时间点的损伤面积越大（R = 0.327，p < 0.01）。我们的研究结果表明，侧方液压冲击损伤诱导的慢性皮质病理程度与急性升高的血浆miR-124-3p水平相关。
