The biomarker value of miRNAs after cerebral ischemia has been suggested by the observation that specific miRNAs have been detected in the blood after ischemic stroke in both animals [
70] and humans [
71]. In addition, some of these miRNAs might be potential biomarkers of ischemic stroke [
71-
73]. As a first attempt to identify miRNAs with prognostic value after cardiac arrest, we performed a proof-of-concept study in which we compared the plasma miRnome of 14 patients with favorable outcome and 14 patients with poor outcome after cardiac arrest [
74]. Using microarrays covering almost 700 miRNAs (miRBase release 12.0), we observed a miRNA biosignature linked to outcome. Among miRNAs differentially expressed between patients with favorable outcome and patients with poor outcome, miR-122 and miR-21 were significant predictors of neurological outcome (areas under the receiver-operating characteristic curve of 0.73 and 0.77, respectively) and mortality (
P < 0.05) at 6 months. We could verify that miR-122 and miR-21 were reliably expressed by neuronal cells, as also shown elsewhere [
75,
76], comforting our working hypothesis that miRNAs originating from dying neurons after cardiac arrest can be measured in the bloodstream. Consistent with this hypothesis was the demonstration that exosomes, which carry miRNAs outside cells, are able to cross the blood-brain barrier [
69]. In addition, disruption of the blood-brain barrier has been shown after cerebral ischemia, which may facilitate the release of neuron-derived miRNAs into the bloodstream [
77]. Sheinerman and colleagues [
78] identified brain-enriched miRNAs in the blood of patients with mild cognitive impairment, an early stage of multiple neurodegenerative diseases. Thus, brain-derived miRNAs present in the bloodstream after cardiac arrest may indicate neurological damage. Since the extent of neurological damage is a critical determinant of post-cardiac arrest recovery, it is expected that circulating miRNAs may have an interesting prognostic value in this setting. A recent study from our group showing that brain-enriched miR-124 is associated with neurological outcome after cardiac arrest confirmed this assumption [
79]. In future studies, the added value of this novel category of biomarkers over existing tools will have to be determined. Also, the sensitivity and specificity of miRNAs, as well as their usefulness for early prediction, will have to outperform current electrophysiological and neuroimaging tools. Finally, the techniques used to quantify miRNAs, which are still time-consuming, will have to be improved, both in terms of reproducibility, rapidity, cost, and standardization.