Livingston Whitney S, Gill Jessica M, Cota Martin R, Olivera Anlys, O'Keefe Jessica L, Martin Christiana, Latour Lawrence L
1 National Institutes of Health, National Institute of Nursing Research , Bethesda, Maryland.
2 Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences , Bethesda, Maryland.
J Neurotrauma. 2017 Feb 15;34(4):853-860. doi: 10.1089/neu.2016.4479. Epub 2016 Aug 30.
Injury to the meninges is not uncommon after traumatic brain injury (TBI), yet minimal research has been directed toward understanding the relevant biology. After a concussive event, the meninges are observed to abnormally enhance on post-contrast magnetic resonance imaging (MRI) in some patients, but not all. The aim of this work is to identify genes differentially expressed in patients with meningeal injury. Patients presenting to the emergency room with suspected TBI received a standard research MRI and blood draw within 48 h of injury. Two groups of patients were included: those with and without abnormal enhancement of the meninges on post-contrast MRI, both without other imaging findings. Groups were compared on microarray gene expression in peripheral blood samples using Affymetrix (Santa Clara, CA) and Partek Genomics Suite (Partek, Inc., St. Louis, MO) software (false discovery rate, <0.05). Forty patients were enrolled with a time from injury to MRI/blood draw of 16.8 h (interquartile range, 7.5-24.1). We observed 76 genes to be differentially expressed in patients with meningeal injury compared to those without, such as receptor for Fc fragment of IgA, multiple C2 domains, transmembrane 2, and G-protein-coupled receptor 27, which have been previously associated with initiating inflammatory mediators, phagocytosis, and other regulatory mechanisms. Post-contrast MRI is able to detect meningeal injury and has a unique biological signature observed through gene expression. These findings suggest that an acute inflammatory response occurs in response to injury to the meninges following a concussion.
创伤性脑损伤(TBI)后,脑膜损伤并不罕见,但针对相关生物学机制的研究却很少。在发生脑震荡后,部分患者在对比增强磁共振成像(MRI)上可见脑膜异常强化,但并非所有患者都如此。本研究旨在确定脑膜损伤患者中差异表达的基因。因疑似TBI就诊于急诊室的患者在受伤后48小时内接受了标准的研究性MRI检查和血液采集。纳入了两组患者:对比增强MRI上脑膜有或无异常强化的患者,两组均无其他影像学表现。使用Affymetrix(加利福尼亚州圣克拉拉)和Partek Genomics Suite(密苏里州圣路易斯市Partek公司)软件,对两组外周血样本中的基因表达进行微阵列比较(错误发现率<0.05)。共纳入40例患者,从受伤到进行MRI检查/血液采集的时间为16.8小时(四分位间距为7.5 - 24.1小时)。我们观察到,与未发生脑膜损伤的患者相比,发生脑膜损伤的患者中有76个基因差异表达,如免疫球蛋白A Fc片段受体、多个C2结构域、跨膜蛋白2和G蛋白偶联受体27,这些基因先前与启动炎症介质、吞噬作用及其他调节机制有关。对比增强MRI能够检测脑膜损伤,并且通过基因表达可观察到独特的生物学特征。这些发现表明,脑震荡后脑膜损伤会引发急性炎症反应。