Meissner Lilja, Gallozzi Micaela, Balbi Matilde, Schwarzmaier Susanne, Tiedt Steffen, Terpolilli Nicole A, Plesnila Nikolaus
1 Department of Neurodegeneration, Royal College of Surgeons in Ireland , Dublin, Ireland .
2 Institute for Stroke and Dementia Research, University of Munich Medical Center , Munich, Germany .
J Neurotrauma. 2016 Apr 15;33(8):713-20. doi: 10.1089/neu.2015.4077. Epub 2015 Dec 23.
MicroRNAs (miRNAs) were recently identified as important regulators of gene expression under a wide range of physiological and pathophysiological conditions. Thus, they may represent a novel class of molecular targets for the management of traumatic brain injury (TBI). In this study, we investigated the temporal profile of miRNA expression during the development of secondary brain damage after experimental TBI. For this purpose, we used a controlled cortical impact model in C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression in the traumatized cortex by microarray analysis during the development of secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780 mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of these, 158 miRNAs were significantly upregulated or downregulated in TBI compared with sham-operated animals, and 52 miRNAs increased more than twofold. We validated the upregulation of five of the most differentially expressed miRNAs (miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially expressed miRNA after TBI, was further investigated by in situ hybridization and was found to be upregulated in neurons within the traumatic penumbra. This study gives a comprehensive picture of miRNA expression levels during secondary contusion expansion after TBI and may pave the way for the identification of novel targets for the management of brain trauma.
微小RNA（miRNA）最近被确定为在广泛的生理和病理生理条件下基因表达的重要调节因子。因此，它们可能代表了一类用于治疗创伤性脑损伤（TBI）的新型分子靶点。在本研究中，我们调查了实验性TBI后继发性脑损伤发展过程中miRNA表达的时间变化情况。为此，我们在C57Bl/6小鼠（n = 6）中使用可控皮质撞击模型诱导皮质挫伤，并在继发性挫伤扩展过程中，即TBI后1、6和12小时，通过微阵列分析创伤皮质中的miRNA表达。在总共分析的780个成熟miRNA序列中，所有实验组均检测到410个。其中，与假手术动物相比，158个miRNA在TBI中显著上调或下调，52个miRNA的增加超过两倍。我们通过定量聚合酶链反应（qPCR）验证了五个差异表达最明显的miRNA（miR-21*、miR-144、miR-184、miR-451、miR-2137）的上调以及四个差异表达最明显的miRNA（miR-107、miR-137、miR-190、miR-541）的下调。TBI后差异表达最明显的miRNA miR-2137通过原位杂交进一步研究，发现在创伤半暗带的神经元中上调。本研究全面描绘了TBI后继发性挫伤扩展过程中miRNA的表达水平，可能为确定脑创伤治疗的新靶点铺平道路。
