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Walsh KB, Zimmerman KD, Zhang X, et al. miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model. J Mol Neurosci. 2021;71(9):1802-1814doi: 10.1007/s12031-021-01815-9.
Walsh, K. B., Zimmerman, K. D., Zhang, X., Demel, S. L., Luo, Y., Langefeld, C. D., Wohleb, E., Schulert, G., Woo, D., & Adeoye, O. (2021). miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model. Journal of molecular neuroscience : MN, 71(9), 1802-1814. https://doi.org/10.1007/s12031-021-01815-9
Walsh, Kyle B, et al. "miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model." Journal of molecular neuroscience : MN vol. 71,9 (2021): 1802-1814. doi: https://doi.org/10.1007/s12031-021-01815-9
Walsh KB, Zimmerman KD, Zhang X, Demel SL, Luo Y, Langefeld CD, Wohleb E, Schulert G, Woo D, Adeoye O. miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model. J Mol Neurosci. 2021 Sep;71(9):1802-1814. doi: 10.1007/s12031-021-01815-9. Epub 2021 Mar 23. PMID: 33755911.
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J Mol Neurosci. 2021 Sep;71(9):1802-1814. doi: 10.1007/s12031-021-01815-9. Epub 2021 Mar 23.

miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model.

Journal of molecular neuroscience : MN

Kyle B Walsh, Kip D Zimmerman, Xiang Zhang, Stacie L Demel, Yu Luo, Carl D Langefeld, Eric Wohleb, Grant Schulert, Daniel Woo, Opeolu Adeoye

Affiliations

  1. University of Cincinnati Gardner Neuroscience Institute, Cincinnati, OH, USA. [email protected].
  2. Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA. [email protected].
  3. Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
  4. Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
  5. University of Cincinnati Gardner Neuroscience Institute, Cincinnati, OH, USA.
  6. Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH, USA.
  7. Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH, USA.
  8. Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
  9. University of Cincinnati Neurobiology Research Center, Cincinnati, OH, USA.
  10. Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  11. Department of Emergency Medicine, Washington University in St. Louis, St. Louis, MO, USA.

PMID: 33755911 DOI: 10.1007/s12031-021-01815-9

Abstract

Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Inflammation after ICH contributes to clinical outcomes, but the relevant molecular mechanisms remain poorly understood. In studies of peripheral leukocyte counts and mRNA-sequencing (mRNA-seq), our group previously reported that monocytes and Interleukin-8 (IL-8) were important contributors to post-ICH inflammation. microRNA (miRNA) are powerful regulators of gene expression and promising therapeutic targets. We now report findings from an integrated analysis of miRNA-seq and mRNA-seq in peripheral blood mononuclear cells (PBMCs) from a swine ICH model. In 10 pigs, one PBMC sample was collected immediately prior to ICH induction and a second 6 h later; miRNA-seq and mRNA-seq were completed for each sample. An aggregate score calculation determined which miRNA regulated the differentially expressed mRNA. Networks of molecular interactions were generated for the combined miRNA/target mRNA. A total of 227 miRNA were identified, and 46 were differentially expressed after ICH (FDR < 0.05). The anti-inflammatory miR-181a was decreased post-ICH, and it was the most highly connected miRNA in the miRNA/mRNA bioinformatic network analysis. miR-181a has interconnected pathophysiology with IL-8 and monocytes; in prior studies, we found that IL-8 and monocytes contributed to post-ICH inflammation and ICH clinical outcome, respectively. miR-181a was a significant mediator of post-ICH inflammation and is promising for further study, including as a potential therapeutic target. This investigation also demonstrated feasible methodology for miRNA-seq/mRNA-seq analysis in swine that is innovative, and with unique challenges, compared with transcriptomics research in more established species.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Keywords: Inflammation; Intracerebral hemorrhage; Preclinical models; RNA-seq; Stroke; Transcriptomics

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