Powers Ciarán J, Dickerson Ryan, Zhang Stacey W, Rink Cameron, Roy Sashwati, Sen Chandan K
Department of Neurological Surgery, The Ohio State Wexner Medical Center, Columbus, Ohio; and
Department of Surgery, The Ohio State Wexner Medical Center, Columbus, Ohio.
Physiol Genomics. 2016 May;48(5):361-6. doi: 10.1152/physiolgenomics.00052.2015. Epub 2016 Mar 4.
Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of hemorrhagic stroke with 30-day mortality between 33 and 45%. Delayed cerebral ischemia (DCI) is the chief cause of morbidity and mortality in patients who survive the initial aSAH. DCI accounts for almost 50% of deaths in patients surviving to treatment of the ruptured aneurysm. The mechanisms for brain injury after aSAH and the brain's response to this injury are not fully understood in humans. MicroRNAs (miRs) are 22- to 25-nucleotide single-stranded RNA molecules that inhibit the expression of specific messenger RNA targets. In this work, miR profiling of human cerebrospinal fluid from eight patients after aSAH was performed daily for 10 days with the goal of identifying changes in miR abundance. Using the nanoString nCounter Expression Assay, we identified two specific clusters of miR that were differentially regulated over time. Quantitative RT-PCR was performed on select miRs from each cluster. The first cluster contained miRs known to be present in blood and decreased in abundance over time. miRs in this group include miR-92a and let-7b. The second cluster contained several poorly characterized miRs that increased in abundance over time. miRs in this group included miR-491. This second cluster of miRs may be released into the CSF by the brain itself as a result of the initial SAH. Temporal changes in the abundance of specific miRs in human CSF after aSAH may provide novel insight into the role of miRs in brain injury and the brain's response.
动脉瘤性蛛网膜下腔出血（aSAH）是出血性卒中的一种严重形式，30天死亡率在33%至45%之间。迟发性脑缺血（DCI）是aSAH初始发作后存活患者发病和死亡的主要原因。DCI占破裂动脉瘤治疗后存活患者死亡人数的近50%。在人类中，aSAH后脑损伤的机制以及大脑对这种损伤的反应尚未完全了解。微小RNA（miRs）是22至25个核苷酸的单链RNA分子，可抑制特定信使RNA靶标的表达。在这项研究中，对8例aSAH患者的脑脊液进行了为期10天的每日miR分析，目的是确定miR丰度的变化。使用nanoString nCounter表达分析，我们确定了两个随时间差异调节的特定miR簇。对每个簇中的选定miR进行了定量RT-PCR。第一个簇包含已知存在于血液中且丰度随时间降低的miR。该组中的miR包括miR-92a和let-7b。第二个簇包含几个特征不明确的miR，其丰度随时间增加。该组中的miR包括miR-491。这第二个miR簇可能是由于最初的SAH而由大脑自身释放到脑脊液中的。aSAH后人类脑脊液中特定miR丰度的时间变化可能为miR在脑损伤和大脑反应中的作用提供新的见解。
