Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up.
Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up.
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DOI：
10.3389/fnagi.2016.00168
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发表时间：
2016
影响因子：
4.8
通讯作者：
Gill J
中科院分区：
文献类型：
--
作者：
Cho YE;Latour LL;Kim H;Turtzo LC;Olivera A;Livingston WS;Wang D;Martin C;Lai C;Cashion A;Gill J
年龄越大，从创伤性脑损伤(TBI)中完全康复的能力越差；然而，解释与年龄相关的风险的性质的数据有限。这项研究是为了确定年龄与脑外伤后基因活性的关系，以及这种生物标记物如何与神经影像表现的变化相关。比较了青年组(19岁至35岁)和老年组(60岁至)在脑外伤后48小时内的全球基因活性，然后在1周内进行随访。在每个时间点，获得并比较磁共振成像(MRI)和计算机断层扫描(CT)的基因表达谱和影像表现。青年组大鼠48h和1周时碱性亮氨酸拉链转录因子2(BACH2)、富亮氨酸重复序列神经元3(LRRN3)、淋巴增强因子结合因子1(LEF1)等炎症调控基因的基因表达显著高于老年组。在老年组中，S100家族基因的活性增加，包括钙结合蛋白P(S100P)和S100钙结合蛋白A8(S100A8)，以前的研究表明这两个基因与颅脑损伤恢复差有关。与年轻组相比，老年组noggin(Nog)基因的活性也降低，noggin基因是转化生长因子-β超家族的成员，与神经康复和神经再生有关。我们将这些被证实的基因表达结果与神经成像联系起来，报告说，在MRI发现与脑外伤相关的损害的老年组中，与年轻组相比，在随访时MRI阴性的可能性较小。综上所述，这些数据表明，年龄影响脑外伤后的基因活性，并表明这种与免疫调节和神经恢复相关的差异活动有助于降低通过神经成像显示的老年患者神经元恢复的可能性。
Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging.