Small extracellular vesicles (sEVs)
miRNAs are promising diagnosis and prognosis
biomarkers for
ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs
miRNA profile of IS patients and a transient
middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs
miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and
sham controls. Among the 1,444 and 1,373
miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37
miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated
miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p,
hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four
miRNAs was further validated by qPCR. Nine of the 20 upregulated
miRNAs in tMCAO mice were also brain-specific or enriched
miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic
brain injury, as their expression increased at 0.5 days after the onset of
ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight
miRNAs in the mouse serum sEVs was unaffected in the
lipopolysaccharide (LPS)-induced
neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs
miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific
miRNAs in serum sEVs after acute
cerebral ischemia, which could be promising candidates directly reflecting the ischemic
brain injury.