Skip to main content
SpringerLink
Log in

Estimation of time-dependent microRNA expression patterns in brain tissue, leukocytes, and blood plasma of rats under photochemically induced focal cerebral ischemia

  • Molecular Cell Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

miRNA expression over different time periods (24 and 48 h) using the quantitative RT-PCR and deep sequencing has been evaluated in a model of photochemically induced thrombosis. A combination of two approaches allowed us to determine the miRNA expression patterns caused by ischemia. Nine miRNAs, including let-7f-5p, miR-221-3p, miR-21-5p, miR-30c-5p, miR-30a-3p, miR-223-3p, miR-23a-3p, miR-22-5p, and miR-99a-5p, were differentially expressed in brain tissue and leukocytes of rats 48 h after onset of ischemia. In addition, six miRNAs were differentially expressed in the brain tissue and blood plasma of rats 24 h after exposure, among which miR-145-3p and miR-375-3p were downregulated and miR-19a-3p, miR-92a-3p, miR-188-5p, and miR-532-5p were upregulated. In our opinion, miR-188-5p and miR-532-5p may be considered to be new potential markers of ischemic injury. The level of miRNA expression tended to increase 48 h after the onset of ischemia in brain tissue and leukocytes, which reflects not only the local response in brain tissue due to inflammation, vascular endothelial dysfunction, and disorders of the permeability of the blood–brain barrier, but also the systemic response of the organism to multifactor molecular processes induced by ischemic injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

miRNA:

microRNA

FC:

fold change (of expression)

МСАО:

middle cerebral artery occlusion

References

  1. Jeyaseelan K., Lim K.Y., Armugam A. 2008. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 39, 959–966.

    Article  CAS  PubMed  Google Scholar 

  2. Di Y., Lei Y., Yu F., Changfeng F., Song W., Xuming M. 2014. MicroRNAs expression and function in cerebral ischemia reperfusion injury. J. Mol. Neurosci. 53, 242–250.

    Article  CAS  PubMed  Google Scholar 

  3. Rink C., Khanna S. 2011. MicroRNA in ischemic stroke etiology and pathology. Physiol. Genomics. 43, 521–528.

    Article  CAS  PubMed  Google Scholar 

  4. Li Y., Liu Y., Wang Z., Hou H., Lin Y., Jiang Y. 2013. MicroRNA: Not far from clinical application in ischemic stroke. ISRN Stroke. 2013, 1–7.

    Article  Google Scholar 

  5. Dharap A., Bowen K., Place R., Li L., Vemuganti R. 2009. Transient focal ischemia induces extensive temporal changes in rat cerebral MicroRNAome. J. Cereb. Blood Flow Metab. 29, 675–687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Long G., Wang F., Li H., Yin Z., Sandip C., Lou Y., Wang Y., Chen C., Wang D.W. 2013. Circulating miR- 30a, miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol. 13, 178.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu D.-Z., Tian Y., Ander B.P., Xu H., Stamova B.S., Zhan X., Turner R.J., Jickling G., Sharp F.R. 2010. Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J. Cereb. Blood Flow Metab. 30, 92–101.

    Article  PubMed  Google Scholar 

  8. Liu F.J., Lim K.Y., Kaur P., Sepramaniam S., Armugam A., Wong P.T.H., Jeyaseelan K. 2013. MicroRNAs involved in regulating spontaneous recovery in embolic stroke model. PLoS ONE. 8, e66393.

    Article  Google Scholar 

  9. Yuan Y., Wang J.Y., Xu L.Y., Cai R., Chen Z., Luo B.Y. 2010. MicroRNA expression changes in the hippocampi of rats subjected to global ischemia. J. Clin. Neurosci. 17, 774–778.

    Article  CAS  PubMed  Google Scholar 

  10. Lee S.-T., Chu K., Jung K.-H., Yoon H.-J., Jeon D., Kang K.-M., Park K.-H., Bae E.-K., Kim M., Lee S.K., Roh J.-K. 2010. MicroRNAs induced during ischemic preconditioning. Stroke. 41, 1646–1651.

    Article  PubMed  Google Scholar 

  11. Lu X.-C.M., Williams A.J., Yao C., Berti R., Hartings J.A., Whipple R., Vahey M.T., Polavarapu R.G., Woller K.L., Tortella F.C., Dave J.R. 2004. Microarray analysis of acute and delayed gene expression profile in rats after focal ischemic brain injury and reperfusion. J. Neurosci. Res. 77, 843–857.

    Article  CAS  PubMed  Google Scholar 

  12. Ziu M., Fletcher L., Rana S., Jimenez D.F., Digicaylioglu M. 2011. Temporal differences in microRNA expression patterns in astrocytes and neurons after ischemic injury. PLoS ONE. 6, e14724.

    Article  Google Scholar 

  13. Zhai F., Zhang X., Guan Y., Yang X., Li Y., Song G., Guan L. 2012. Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats. Neural Regen. Res. 7, 917–923.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Hallenbeck J.M., Dutka A.J., Tanishima T., Kochanek P.M., Kumaroo K.K., Thompson C.B., Obrenovitch T.P., Contreras T.J. 1986. Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke. 17, 246–253.

    Article  CAS  PubMed  Google Scholar 

  15. Ishikawa M., Zhang J.H., Nanda A., Granger D.N. 2004. Inflammatory responses to ischemia and reperfusion in the cerebral microcirculation. Front. Biosci. 9, 1339–1347.

    Article  CAS  PubMed  Google Scholar 

  16. Moore D.F., Li H., Jeffries N., Wright V., Cooper R.A., Elkahloun A., Gelderman M.P., Zudaire E., Blevins G., Yu H., Goldin E., Baird A.E. 2005. Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: A pilot investigation. Circulation. 111, 212–221.

    Article  CAS  PubMed  Google Scholar 

  17. Grond-Ginsbach C., Hummel M., Wiest T., Horstmann S., Pfleger K., Hergenhahn M., Hollstein M., Mansmann U., Grau A.J., Wagner S. 2008. Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke. J. Neurol. 255, 723–731.

    Article  CAS  PubMed  Google Scholar 

  18. Creighton C.J., Reid J.G., Gunaratne P.H. 2009. Expression profiling of microRNAs by deep sequencing. Brief. Bioinform. 10, 490–497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang C., Pan Y., Cheng B., Chen J., Bai B. 2014. Identification of conserved and novel microRNAs in cerebral ischemia–reperfusion injury of rat using deep sequencing. J. Mol. Neurosci. 54, 671–683.

    Article  CAS  PubMed  Google Scholar 

  20. Powers C.J., Dickerson R., Zhang S.W., Rink C., Roy S., Sen C.K. 2016. Human cerebrospinal fluid microRNA: Temporal changes following subarachnoid hemorrhage. Physiol. Genomics. 48, 361–366.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Watson B.D., Dietrich W.D., Busto R., Wachtel M.S., Ginsberg M.D. 1985. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann. Neurol. 17, 497–504.

    Article  CAS  PubMed  Google Scholar 

  22. Dweep H., Gretz N. 2015. miRWalk2.0: A comprehensive atlas of microRNA-target interactions. Nat. Methods 12, 697.

    Article  CAS  PubMed  Google Scholar 

  23. Kozomara A., Griffiths-Jones S. 2014. miRBase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42, D68–D73.

    Article  CAS  PubMed  Google Scholar 

  24. Langmead G., Trapnell C., Pop M., Salzberg S. 2009. Ultrafast and memory-efficient of short DNA sequences to the human genome. Genome Biol. 10, R25.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., Marth G., Abecasis G., Durbin R. 2009. The sequence alignment/map format and SAMtools. Bioinformatics. 25, 2078–2079.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gu W., Brännström T., Wester P. 2000. Cortical neurogenesis in adult rats after reversible photothrombotic stroke. J. Cereb. Blood Flow Metab. 20, 1166–1173.

    Article  CAS  PubMed  Google Scholar 

  27. Gu W., Brännströ m T., Jiang W., Bergh A., Wester P. 2001. Vascular endothelial growth factor-A and -C protein up-regulation and early angiogenesis in a rat photothrombotic ring stroke model with spontaneous reperfusion. Acta Neuropathol. 102, 216–226.

    CAS  PubMed  Google Scholar 

  28. Hu X.-L., Olsson T., Johansson I.-M., Brännström T., Wester P. 2004. Dynamic changes of the anti- and proapoptotic proteins Bcl-w, Bcl-2, and Bax with Smac/Diablo mitochondrial release after photothrombotic ring stroke in rats. Eur. J. Neurosci. 20, 1177–1188.

    Article  PubMed  Google Scholar 

  29. Hu X., Johansson I.-M., Brännström T., Olsson T., Wester P. 2002. Long-lasting neuronal apoptotic cell death in regions with severe ischemia after photothrombotic ring stroke in rats. Acta Neuropathol. 104, 462–470.

    CAS  PubMed  Google Scholar 

  30. Ritter L.S., Orozco J.A., Coull B.M., McDonagh P.F., Rosenblum W.I. 2000. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke. 31, 1153–1161.

    Article  CAS  PubMed  Google Scholar 

  31. Hallenbeck J.M. 1996. Significance of the inflammatory response in brain ischemia. Acta Neurochir. Suppl. 66, 27–31.

    CAS  PubMed  Google Scholar 

  32. Wang Y., Huang J., Ma Y., Tang G., Liu Y., Chen X., Zhang Z., Zeng L., Wang Y., Ouyang Y.-B., Yang G.-Y. 2015. MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4. J. Cereb. Blood Flow Metab. 35, 1977–1984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lopez-Ramirez M.A., Reijerkerk A., de Vries H.E., Romero I.A. 2016. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation. FASEB J. 1–11.

    Google Scholar 

  34. Yin K.-J., Deng Z., Huang H., Hamblin M., Xie C., Zhang J., Chen Y.E. 2010. miR-497 regulates neuronal death in mouse brain after transient focal cerebral ischemia. Neurobiol. Dis. 38, 17–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Selvamani A., Sathyan P., Miranda R.C., Sohrabji F. 2012. An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PLoS ONE. 7, e32662.

    Article  Google Scholar 

  36. Hu G., Gong A.-Y., Liu J., Zhou R., Deng C., Chen X.-M. 2010. miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G542–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Buller B., Liu X., Wang X., Zhang R.L., Zhang L., Hozeska-Solgot A., Chopp M., Zhang Z.G. 2010. MicroRNA-21 protects neurons from ischemic death. FEBS J. 277, 4299–4307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Haneklaus M., Gerlic M., O’Neill L.A.J., Masters S.L. 2013. miR-223: Infection, inflammation and cancer. J. Intern. Med. 274, 215–226.

    Article  CAS  PubMed  Google Scholar 

  39. Johnnidis J.B., Harris M.H., Wheeler R.T., Stehling-Sun S., Lam M.H., Kirak O., Brummelkamp T.R., Fleming M.D., Camargo F.D. 2008. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 451, 1125–1129.

    Article  CAS  PubMed  Google Scholar 

  40. Chen Q., Wang H., Liu Y., Song Y., Lai L., Han Q., Cao X., Wang Q. 2012. Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1ß production in macrophages by targeting STAT3. PLoS ONE. 7, e42971.

    Article  Google Scholar 

  41. Harraz M.M., Eacker S.M., Wang X., Dawson T.M., Dawson V.L. 2012. MicroRNA-223 is neuroprotective by targeting glutamate receptors. Proc. Natl. Acad. Sci. U. S. A. 109, 18962–18967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tan K.S., Armugam A., Sepramaniam S., Lim K.Y., Setyowati K.D., Wang C.W., Jeyaseelan K. 2009. Expression profile of microRNAs in young stroke patients. PLoS ONE. 4, e7689.

    Article  Google Scholar 

  43. Zhao H., Tao Z., Wang R., Liu P., Yan F., Li J., Zhang C., Ji X., Luo Y. 2014. MicroRNA-23a-3p attenuates oxidative stress injury in a mouse model of focal cerebral ischemia–reperfusion. Brain Res. 1592, 65–72.

    Article  CAS  PubMed  Google Scholar 

  44. Yu H., Wu M., Zhao P., Huang Y., Wang W., Yin W. 2015. Neuroprotective effects of viral overexpression of microRNA-22 in rat and cell models of cerebral ischemia–reperfusion injury. J. Cell. Biochem. 116, 233–241.

    Article  CAS  PubMed  Google Scholar 

  45. Tao Z., Zhao H., Wang R., Liu P., Yan F., Zhang C., Ji X., Luo Y. 2015. Neuroprotective effect of microRNA-99a against focal cerebral ischemia–reperfusion injury in mice. J. Neurol. Sci. 355, 113–119.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kulakov Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Healthcare of the Russian Federation, Moscow, 117997, Russia

    V. A. Gusar & A. V. Timofeeva

  2. Scientific Center of Children’s Health, Ministry of Healthcare of the Russian Federation, Moscow, 119991, Russia

    V. A. Gusar, A. V. Timofeeva, I. S. Zhanin & V. G. Pinelis

  3. Sechenov First Moscow State Medical University, Moscow, 119991, Russia

    I. S. Zhanin

  4. Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia

    S. I. Shram

Authors
  1. V. A. Gusar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Timofeeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. S. Zhanin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. I. Shram
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. G. Pinelis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. A. Gusar.

Additional information

Original Russian Text © V.A. Gusar, A.V. Timofeeva, I.S. Zhanin, S.I. Shram, V.G. Pinelis, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 4, pp. 683–695.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gusar, V.A., Timofeeva, A.V., Zhanin, I.S. et al. Estimation of time-dependent microRNA expression patterns in brain tissue, leukocytes, and blood plasma of rats under photochemically induced focal cerebral ischemia. Mol Biol 51, 602–613 (2017). https://doi.org/10.1134/S0026893317040100

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893317040100

Keywords

Search

Navigation