1 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine , Baltimore, Maryland.
2 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University , Baltimore, Maryland.
J Neurotrauma. 2018 Jan 15;35(2):353-361. doi: 10.1089/neu.2017.5009. Epub 2017 Nov 17.
At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. Various biological components such as lipids, circulating mRNA, and miRNA, could potentially be detected using advanced techniques such as next-generation sequencing and mass spectroscopy. Therefore, plasma analysis is an attractive approach with which to diagnose and treat brain injuries. Subacute changes in plasma microRNA (miRNA) and lipid composition for sphingolipids were evaluated in a murine model of mild-to-moderate bTBI using next-generation sequencing and mass spectroscopy respectively. Animals were exposed at 17, 17 × 3, and 20 psi blast intensities using a calibrated blast simulator. Plasma lipid profiling demonstrated decreased C18 fatty acid chains of sphingomyelins and increased ceramide levels when compared with controls. Plasma levels of brain-enriched miRNA, miR-127 were increased in all groups while let-7a, b, and g were reduced in the 17 × 3 and 20 psi groups, but let 7d was increased in the 17 psi group. The majority of the miRs and lipids are highly conserved across different species, making them attractive to explore and potentially employ as diagnostic markers. It is tempting to speculate that sphingolipids, miR-128, and the let-7 family could predict mTBI, while a combination of miR-484, miR-122, miR-148a, miR-130a, and miR-223 could be used to predict the overall status of injury following blast injury.
目前，缺乏准确可靠的生物标志物来确定爆炸性创伤性脑损伤 (bTBI) 的存在、严重程度或预后。迫切需要建立能够检测 mbTBI 的准确可靠的生物标志物。目前，尚无研究确定 bTBI 不同严重程度下 miRNA 和脂质的变化。各种生物成分，如脂质、循环 mRNA 和 miRNA，可能可以使用下一代测序和质谱等先进技术进行检测。因此，血浆分析是一种有吸引力的诊断和治疗脑损伤的方法。使用下一代测序和质谱分别评估了轻度至中度 bTBI 小鼠模型中血浆 microRNA (miRNA) 和脂质组成的亚急性变化。动物在 17、17×3 和 20 psi 爆震强度下使用校准爆震模拟器暴露。与对照组相比，血浆脂质谱显示鞘磷脂的 C18 脂肪酸链减少，神经酰胺水平升高。与对照组相比，所有组的脑富集 miRNA miR-127 水平均升高，而 let-7a、b 和 g 在 17×3 和 20 psi 组中降低，但 17 psi 组中的 let-7d 升高。大多数 miRs 和脂质在不同物种中高度保守，这使它们成为有吸引力的探索对象，并可能被用作诊断标志物。推测鞘磷脂、miR-128 和 let-7 家族可能预测 mTBI，而 miR-484、miR-122、miR-148a、miR-130a 和 miR-223 的组合可用于预测爆震伤后损伤的整体状态。
