Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126

Transl Stroke Res. 2015 Dec;6(6):478-84. doi: 10.1007/s12975-015-0429-3. Epub 2015 Oct 9.


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.

Keywords: Biomarker; Exosome; Focal cerebral ischemia; Reperfusion injury; miR-126.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Brain Ischemia / blood
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Exosomes / metabolism*
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / metabolism*
  • Rats
  • Rats, Wistar


  • Biomarkers
  • MIRN126 microRNA, rat
  • MicroRNAs