Circulating miRNAs Associated With 3-Month Outcome in Patients With Acute Ischemic Stroke

BACKGROUND AND OBJECTIVES: Post-ischemic stroke (IS) outcomes vary widely among individuals, independently of clinical factors. This variability could be related to epigenetic mechanisms that regulate biological processes involved in recovery after ischemia. While several microRNAs (miRNAs) and their target genes are implicated in the pathophysiology of IS, their role in functional outcomes remains unclear. Our aim is to identify potential miRNAs associated with the 3-month outcome in patients with IS. METHODS: A discovery study was performed in patients with acute IS assessed at Hospital del Mar of Barcelona from 2009 to 2018. Main inclusion criteria were initial NIH Stroke Scale (NIHSS) score >2, hospital admission within 24 hours of IS onset, and previous functional independence. Poor 3-month outcome was defined as a modified Rankin Scale score >2. We performed miRNA next-generation sequencing on plasma samples obtained within 24 hours and performed a differential expression analysis for 2,083 miRNAs using the DESeq2 package. A replication stage was performed using real time-PCR in another multicenter cohort, with equivalent inclusion criteria and multivariate regression models. We also performed enrichment pathways analyses in both phases. RESULTS: < 0.05, fold change >1.7): miR-376c-3p, miR-4463, miR-199a-3p, miR-584-5p, and miR-134-5p. DISCUSSION: We identified 5 miRNAs overexpressed in patients with poor 3-month outcomes after IS, which could be involved in biological processes such as cognition, neuronal morphogenesis, and TGF-β response, suggesting a potential role in brain recovery. These findings were not evaluated in infratentorial and lacunar strokes, which limits generalizability in these particular subtypes. Further investigation is needed to explore potential applicability of these findings.