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Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126

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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.

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Acknowledgments

Thanks to Drs. Xandra Breakefield and Balaj Leonora for expert advice on exosomes.

Author information

Authors and Affiliations

  1. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China

    Fan Chen, Yi Liu & Xunming Ji

  2. Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Fan Chen, Yang Du, Elga Esposito, Yi Liu, Shuzhen Guo, Xiaoying Wang, Eng H. Lo & Changhong Xing

  3. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Yang Du

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  1. Fan Chen
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Correspondence to Changhong Xing or Xunming Ji.

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Ethical approval

All animal experiments were approved by the MGH Institutional Animal Care and Use Committee in accordance with the NIH Guide for the Care and Use of Laboratory Animals. This article does not contain any studies with human participants performed by any of the authors.

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Funding

Supported in part by grants from NIH and National Natural Science Foundation of China.

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Chen, F., Du, Y., Esposito, E. et al. Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126. Transl. Stroke Res. 6, 478–484 (2015). https://doi.org/10.1007/s12975-015-0429-3

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  • DOI: https://doi.org/10.1007/s12975-015-0429-3

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