Abstract
miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P<0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p, miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 (P<0.001), 0.950 (P<0.001) and 0.843 (P<0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH.
Highlights
Subarachnoid haemorrhage (SAH) typically results from a ruptured aneurysm and is a small (5%) but catastrophic subset of stroke [1]
To select candidate miRNA biomarkers for SAH patients, we first performed initial genome-wide miRNA screening of two pools of serum samples derived from SAH patients and healthy controls by miRNA microarray analysis
Discussion miRNAs are reported to act as regulators of protein-coding gene expression and have been shown to affect several important biological processes that are associated with traumatic brain injury-induced pathophysiology, including apoptosis and neuronal plasticity [21]
Summary
Subarachnoid haemorrhage (SAH) typically results from a ruptured aneurysm and is a small (5%) but catastrophic subset of stroke [1]. One major determinant of the outcome after treatment of patients with SAH is the characteristics of the initial haemorrhage at admission, which significantly determines the neurological status of patients. This is an important cause of early brain injury (EBI) and early cerebral vasospasm (CVs) after SAH in humans and may be associated with delayed cerebral ischaemia (DCI) [2]. Further threats to recovery are re-bleeding, subsequent delayed vasospasm and the complexity of therapeutic intervention. The complete pathogenesis of EBI and CVs remains incompletely understood, and no effective therapeutic method is available to adequately address these processes
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