Abstract WMP30: Expansion Of Plasma Micrornas Over The First Month Following Human Stroke

Introduction: Stroke induces changes in plasma microRNA (miRNA) expression in the first 24hrs post-injury, but few have characterized miRNA expression during the early recovery phase. Hypothesis: We hypothesized that plasma miRNA expression would evolve over the first month post-stroke with fewer significantly altered miRNAs over time as inflammation and edema resolve. Methods: Longitudinal samples were collected 5, 15, and 30 days post-stroke from 2 studies (BIOREC and MORSE, n=55 combined at each time point) and compared to controls matched for age, sex, race and cardiovascular comorbidities. Stroke samples collected on average around day 15 from a second study (CPASS, n=48) were also compared to matched controls and used as a validation cohort. MiRNA expression was determined with OpenArray qRT-PCR quantifying 758 miRNAs. Significant miRNAs had a corrected p-value less than 0.05 and fold-change greater than |1.5|. Results: Eight miRNAs remained significantly altered across all 3 time points in the discovery cohort and in the day 15 validation cohort (decreased expression compared to controls: miR-101-3p, miR-107, miR-16-2-3p, miR-19a-3p, miR-19b-3p, and miR-26b-5p; increased expression: miRNA-199a-3p and miR-652-3p). The number of significant miRNAs more than doubled from post-stroke day 5 to days 15 and 30 (19, 53, and 45 miRNAs respectively in BIOREC/MORSE, 49 miRNAs at day 15 in CPASS). At day 5 most significant miRNAs (14/19) showed decreased expression compared to controls whereas by day 30 most demonstrated increased expression (36/45). Many of the significant miRNAs, including miR-107 and miR-652-3p, and many others at days 15 and 30 were enriched in brain or CSF in prior studies. Conclusions: While several miRNAs show significant change in expression consistently from 5 to 30 days post-stroke, there is also an expansion of significant miRNAs at days 15 and 30. This expansion includes many miRNAs enriched in brain or CSF and could represent a shift from inflammation to neural repair processes, but this requires further study.