title: Genome-Wide Analysis of the Circulating miRNome After Cerebral Ischemia Reveals a Reperfusion-Induced MicroRNA Cluster.
abstract: Circulating microRNAs (miRNAs) are emerging biomarkers for stroke because of their high stability in the bloodstream and association with pathophysiologic conditions. However, the circulating whole-genome miRNAs (miRNome) has not been characterized comprehensively in the acute phase of stroke.
  
  
  
  We profiled the circulating miRNome in mouse models of acute ischemic and hemorrhagic stroke by next-generation sequencing. Stroke models were compared with sham-operated and naive mice to identify deregulated circulating miRNAs. Top-ranked miRNAs were validated and further characterized by quantitative reverse transcription polymerase chain reaction.
  
  
  
  We discovered 24 circulating miRNAs with an altered abundance in the circulation 3 hours after ischemia, whereas the circulating miRNome was not altered after intracerebral hemorrhage compared with sham-operated mice. Among the upregulated miRNAs in ischemia, the top-listed miR-1264/1298/448 cluster was strongly dependent on reperfusion in different ischemia models. A time course experiment revealed that the miR-1264/1298/448 cluster peaked in the circulation around 3 hours after reperfusion and gradually decreased thereafter.
  
  
  
  Alteration of the miRNome in the circulation is associated with cerebral ischemia/reperfusion, but not hemorrhage, suggesting a potential to serve as biomarkers for reperfusion in the acute phase. The pathophysiological role of reperfusion-inducible miR-1264/1298/448 cluster, which is located on chromosome X within the introns of the serotonin receptor HTR2C, requires further investigation.
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlmann
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Eva
authors.initials: E
authors.lastname: Mracsko
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Ehsan
authors.initials: E
authors.lastname: Javidi
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Sarah
authors.initials: S
authors.lastname: Lamble
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Ana
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Agnes
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.).
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Glatting
authors.affiliation: From the Department of Neurology, University Heidelberg, Germany (S.U., E.M., E.J., R.V.); High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom (S.L., A.T.); Genomics Proteomics Core Facility HUSAR Bioinformatics Lab, German Cancer Research Center (DKFZ), Heidelberg, Germany (A.H.-W., K.-H.G.); Division of Brain Sciences, Imperial College London, United Kingdom (R.V.). roland.veltkamp@imperial.nhs.uk.
authors.forename: Roland
authors.initials: R
authors.lastname: Veltkamp
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002545:Brain Ischemia / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000235:genetics; D055106:Genome-Wide Association Study; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D005810:Multigene Family; D015424:Reperfusion; D015427:Reperfusion Injury / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarkers; cerebral hemorrhage; microRNAs; reperfusion; serotonin receptor