Emerging data suggest that exosomal
microRNA (
miRNA) may provide potential
biomarkers in
acute ischemic stroke. However, the effects of
ischemia-reperfusion on total versus exosomal
miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal
cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to
oxygen-
glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal
cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of
infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-
ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient
ischemia. Serum miR-126 levels appeared to differ in permanent versus transient
ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent
ischemia but not transient
ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient
ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent
ischemia from milder injury after transient
ischemia.