To investigate the role of microRNAs as super-early biomarkers in acute ischemic stroke (AIS).

This review was conducted in accordance with the PRISMA statement recommendations. Three databases were searched (Pubmed, Scopus, and Cochrane) for case-control studies comparing the expression of microRNAs in AIS patients and healthy controls. Risk of bias was computed using the QUADAS-2 Scale tool. The review protocol was registered in PROSPERO (CRD42023454012).

A total of 186 articles were screened and 6 full-text articles were included in this review, involving 441 AIS and 307 controls. Samples were obtained from blood in three studies, plasma in two studies, and serum in one study. All studies utilized RT-qPCR as quantification method. One study included only patients with large artery atherosclerosis. Eleven microRNAs were found to be overexpressed and seven underexpressed in AIS. No single microRNA was validated in two separate studies. The misexpressed microRNAs were associated with inflammation, platelet activation, angiogenesis, and apoptosis. Two studies followed the temporal expression of microRNAs. miR-125b-5p and miR-143-3p (inflammation, angiogenesis, and apoptosis) normalized at 90 days. miR-125a-5p (angiogenesis) remained elevated. The heterogeneity in temporal sampling and microRNAs detected did not allow to perform a quantitative analysis. Qualitative analysis of each study revealed an overall moderate risk of bias.

This review suggests the promising potential role of microRNAs as adjuvant tool in the early diagnosis of AIS. Further larger studies are needed to corroborate these findings and discover a reliable and reproducible biomarker.