The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest

Abstract

IntroductionEarly prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability.MethodsWe included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5).ResultsAt 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively.ConclusionsThe brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

“…Patients with high levels of miR-124-3p were also at a higher risk for death (HR: 1.63; 95% CI: 1.37-1.93). These findings confirmed the results of Gilje et al study [44]. Interestingly, therapeutic hypothermia did not affect the circulating levels of miR-124-3p.…”

“…Only one study measured miRNA levels at time of arrest [47]. Other studies measured circulating miRNAs 24-48 h post-ROSC [43][44][45]48]. Table 1 summarizes miRNAs that have been identified as potential biomarkers predicting outcome in studies on patients with out-of-hospital-cardiac arrest.…”

“…Increased levels of circulating miR-122, miR-21 and NSE were also significantly associated with mortality (p = 0.02, 0.02 and <0.001, respectively). Another study prospectively followed 65 OHCA patients treated with hypothermia, and found that admission levels of miR-123 to be elevated tenfold in OHCA patients compared with age-and sex-matched healthy controls (n = 10) [44]. miR-124 was significantly elevated in patients with poor outcomes (CPC: 3-5; p < 0.0001) at 24 h (AUC: 0.87; 95% CI: 0.79-0.96) and at 48 h (AUC: 0.89; 95% CI: 0.80-0.97).…”

Temporal Profile of Circulating microRNAs after Global Hypoxia-Ischemia in Newborn Piglets

“…MiR-124 is the most abundant miRNA in the brain. It plays numerous roles in neuronal proliferation, apoptosis and cell death, and has been proposed as a marker of brain damage after stroke and cardiac arrest in adults [12,13]. MiR-125b is highly enriched in the brain and has been put forward as a potential marker of acute stroke in adults [11,14].…”

A study of microRNAs from dried blood spots in newborns after perinatal asphyxia: a simple and feasible biosampling method

“…It has been shown to influence neurodevelopment by triggering brain-specific alternative pre-mRNA splicing (19). Additionally, miRNA 124 has been shown to predict neurological outcome following cardiac arrest in adults (20). MiRNA 155 has been shown to be involved in microglia-mediated immune response (21).…”