Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126

• DOI: 10.1007/s12975-015-0429-3
• Publication Date: 2015-10-09T01:04:38Z
• Authors: Fan Chen; Yang Du; Elga Esposito; Yi Liu; Shuzhen Guo; Xiaoying Wang; Eng H. Lo; Changhong Xing; Xunming Ji
• Keywords: Male; 0301 basic medicine; Brain; Endothelial Cells; Exosomes; Brain Ischemia; Rats; Disease Models, Animal; MicroRNAs; 03 medical and health sciences; Animals; Humans; Rats, Wistar; Biomarkers; Cells, Cultured

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.