title: Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126.
abstract: 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.
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China.|Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA.|Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Elga
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China.|Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, USA. Xing.Changhong@mgh.harvard.edu.
authors.forename: Changhong
authors.initials: C
authors.lastname: Xing
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China. jixunming@vip.163.com.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; C571458:MIRN126 microRNA, rat; D035683:MicroRNAs
keywords: Biomarker; Exosome; Focal cerebral ischemia; Reperfusion injury; miR-126