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Effect of intravenous injection of antagomiR-1 on brain ischemia

  • Anis Talebi
  • Mehdi Rahnema
  • Mohammad Reza BigdeliEmail author
Original Article
  • 9 Downloads

Abstract

Stroke is one of the leading causes of death in the world, but the underlying molecular mechanism of this disease remains elusive, thus it will be great challenges to finding appropriate protection. MicroRNAs are short, single-stranded, non-coding RNAs and recent studies have shown that they are aberrantly expressed in ischemic condition. Due to the fact that miR-1 has harmful effects on neural damages during brain ischemia, limited miR-1 has been proven to be protective in middle cerebral artery occlusion (MCAO). Here, the possible positive effect of intravenous injection of antagomiR-1 as a post-ischemic treatment on neurological deficits, infarct volume, brain edema and blood–brain barrier (BBB) permeability was evaluated. The rats were divided randomly into three experimental groups, each with 21 animals. MCAO surgery was performed on all groups and one hour later, 0.1 ml normal saline, 0.1 ml rapamycin and 300 pmol/g miR-1 antagomir (soluble in 0.1 ml normal saline), were injected intravenously into control, positive control and treatment group, respectively. After 24 h, neurologic deficits score, infarct volume, brain edema and BBB permeability were measured. The results indicated that post-treatment with miR-1 antagomir significantly improved neurological deficits and reduced infarction volume, brain edema, and BBB permeability. These data proved that there is a positive effects of antagomiR-1 on ischemic neuronal injury and neurological impairment. Due to the fact that microRNAs are able to protect the brain, it would be a promising therapeutic approach to stroke treatment.

Keywords

miR-1 AntagomiR Stroke NDS Edema BBB Infarct volume 

Notes

Acknowledgements

This work was performed as a PhD project supported financially by Department of Biology of Islamic Azad University-Zanjan, Faculty of life Sciences and biotechnology of Shahid Beheshti University, and Council for Stem Cell Sciences and Technologies. We also thank Dr Salma Ahmadloo for reviewing our research paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All the international, national, and/or institutional applicable guidelines for the care and use of animals were followed. All the animal procedures performed in this research were in accordance with the ethical standards of the institution at which the study was conducted. This article does not contain any studies performed on human participants by any of the authors.

References

  1. 1.
    Sandercock P, Berge E, Dennis M, Forbes J, Hand P, Kwan J, Lewis S, Lindley R, Neilson A, Wardlaw J (2004) Cost-effectiveness of thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke assessed by a model based on UK NHS costs. Stroke 35(6):1490–1497CrossRefGoogle Scholar
  2. 2.
    Thomalla G, Sobesky J, Köhrmann M, Fiebach JB, Fiehler J, Weber OZ, Kruetzelmann A, Kucinski T, Rosenkranz M, Röther J, Schellinger PD (2007) Two tales: hemorrhagic transformation but not pa.renchyml hemorrhage after thrombolysis is related to severity and duration of ischemia-MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours. Stroke 38(2):313–318CrossRefGoogle Scholar
  3. 3.
    Christensen M, Schratt GM (2009) MicroRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases. Neurosci Lett 466(2):55–62CrossRefGoogle Scholar
  4. 4.
    Blakeley JO, Llinas RH (2007) Thrombolytic therapy for acute ischemic stroke. J Neurol Sci 261:55–62CrossRefGoogle Scholar
  5. 5.
    Xu L, Ouyang Y, Xiong X, Stary CM, Giffard RG (2015) Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Exp Neurol 264:1–7CrossRefGoogle Scholar
  6. 6.
    Negrini M, Nicoloso MS, Calin GA (2009) MicroRNAs and cancer—new paradigms in molecular oncology. Curr Opin Cell Biol 21:470–479CrossRefGoogle Scholar
  7. 7.
    Zhao Y, Ransom JF, Li A, Vedantham V, Drehle MV, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA12. Cell 129:303317CrossRefGoogle Scholar
  8. 8.
    Carleton M, Cleary MA, Linsley PS (2007) MicroRNAs and cell cycle regulation. Cell Cycle 6:21272132CrossRefGoogle Scholar
  9. 9.
    Yang Y, Sandhu HK, Zhi F, Hua F, Wu M, Xia Y (2015) Effects of hypoxia and ischemia on microRNAs in the brain. Curr Med Chem 22(10):1292–1301CrossRefGoogle Scholar
  10. 10.
    Jeyaseelan K, Lim KM, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39(3):959–966CrossRefGoogle Scholar
  11. 11.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866CrossRefGoogle Scholar
  12. 12.
    Hernando E (2007) microRNAs and cancer: role in tumorigenesis, patient classification and therapy. Clin Transl Oncol 9(3):155–160CrossRefGoogle Scholar
  13. 13.
    Liu DZ, Tian Y, Ander BP, Xu H, Stamova BS, Zhan X, Turner RG (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101CrossRefGoogle Scholar
  14. 14.
    Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang D (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233CrossRefGoogle Scholar
  15. 15.
    Varendi K, Kumar A, Härma M, Andressoo J (2014) miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF.Cell. Mol. Life Sci 71:4443–4456CrossRefGoogle Scholar
  16. 16.
    Miura P, Amirouche A, Clow C, Belanger G, Jasmin B (2012) Brain-derived neurotrophic factor expression is repressed during myogenic differentiation by miR-206. J Neurochem 120:230–238CrossRefGoogle Scholar
  17. 17.
    Timmusk T, Persson H, Metsis M (1994) Analysis of transcriptional initiation and translatability of brain-derived neurotrophic factor mRNAs in the rat brain. Neurosci Lett 177:27–31CrossRefGoogle Scholar
  18. 18.
    Jeyaseelan K, Lim KY, Armugam A (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39:959–966CrossRefGoogle Scholar
  19. 19.
    Shan ZX, Lin QX, Fu YH, Deng CY, Zhou ZL, Zhu JN, Liu XY, Zhang YY, Li Y, Lin SG, Yu XY (2009) Upregulated expression of miR-1/miR-206 in a rat model of myocardial infarction. Biochem Biophys Res Commun 381:597–601CrossRefGoogle Scholar
  20. 20.
    Selvamani A, Sathyan P, Miranda RC, Sohrabji F (2012) Anantagomir to microRNA let7f promotes neuroprotection in an ischemic stroke model. PLoS ONE 7(2):e32662CrossRefGoogle Scholar
  21. 21.
    Zhang Y, Zhang L, Chu W, Wang B, Zhang J, Zhao M, Li X, Li B, Lu Y, Yang B, Shan H (2010) Tanshinone IIA inhibits miR-1 expression through p38 MAPK signal pathway in post-infarction rat cardiomyocytes. Cell Physiol Biochem 26:991–998CrossRefGoogle Scholar
  22. 22.
    Chang CHY, Lui TN, Lin JY, Lin YL, Hsing CH, Wang JJ, Chen RM (2016) Roles of microRNA1 in hypoxiainduced apoptotic insults to neuronal cells. Arch Toxicol 90(1):191–202CrossRefGoogle Scholar
  23. 23.
    Erlich S, Alexandrovich A, Shohami E, Pinkas-Kermarski R (2007) Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiol Dis 26:86–93CrossRefGoogle Scholar
  24. 24.
    Santos RX, Correia SC, Cardoso S, Carvalho C, Santos MS, Moreira PI (2011) Effects of rapamycin and TOR on aging and memory: implications for Alzheimer’s disease. J Neurochem 117:927–936CrossRefGoogle Scholar
  25. 25.
    Malagelada C, Jin ZH, Jackson-Lewis V, Przedborski S, Greene LA (2010) Rapamycin protects against neuron death in vitro and in vivo models of Parkinson’s disease. J Neurosci 30:1166–1175CrossRefGoogle Scholar
  26. 26.
    Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl Th, Manoharan M, Stoffle M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689CrossRefGoogle Scholar
  27. 27.
    Bigdeli MR, Sohrab Hajizadeh S, Froozandeh M, Heidarianpour A, Rasoulian B, Asgari AR, Pourkhalili KH, Khoshbaten A (2008) Normobaric hyperoxia induces ischemic tolerance and upregulation of glutamate transporters in the rat brain and serum TNF-α level. Exp Neurol 212:298–306CrossRefGoogle Scholar
  28. 28.
    Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91CrossRefGoogle Scholar
  29. 29.
    Liu P, Zhang R, Liu D, Wang J, Yuan Ch, Zhao X, Li Y, Ji X, Chi T, Zou L (2018) Time-course investigation of blood–brain barrier permeability and tight junction protein changes in a rat model of permanent focal ischemia. J Physiol Sci 68(2):121–127CrossRefGoogle Scholar
  30. 30.
    Bigdeli MR, Hajizadeha S, Froozandeh M, Rasoulian B, Heidarianpour A, Khoshbaten A (2007) Prolonged and intermittent normobaric hyperoxia induce different degrees of ischemic tolerance in rat brain tissue. Brain Res 1152:228–233CrossRefGoogle Scholar
  31. 31.
    Aboutaleb N, Shamsaei N, Khaksari M, Erfani S, Rajabi H, Nikbakht F (2015) Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation. J Physiol Sci 65(5):435–443CrossRefGoogle Scholar
  32. 32.
    Yin KJ, Hamblin M, Chen YE (2014) Non-coding RNAs in cerebral endothelial pathophysiology: emerging roles in stroke. Neurochem Int 77:9–16CrossRefGoogle Scholar
  33. 33.
    Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139CrossRefGoogle Scholar
  34. 34.
    Williams AE (2008) Functional aspects of animal microRNAs. Cell Mol Life Sci 65:545–562CrossRefGoogle Scholar
  35. 35.
    Dharap A, Bowen K, Place R, Li L, Vemoganti R (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab 29:675–687CrossRefGoogle Scholar
  36. 36.
    Liu DZ, Tian Y, Ander BP, XU H, Stamova BH, Zhan X, Turner RJ, Jickling G, Sharp FR (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101CrossRefGoogle Scholar
  37. 37.
    Lee YJ, Johnson KR, Hallenbeck JM, Meuth SG (2012) Global protein conjugation by ubiquitin-like-modifiers during ischemic stress is regulated by microRNAs and confers robust tolerance to ischemia. PLoS ONE 7(10):e47787CrossRefGoogle Scholar
  38. 38.
    Li D, Liu Y (2015) MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5). FEBS Lett 589:68–76CrossRefGoogle Scholar
  39. 39.
    Tang Y, Zheng J, Sun Y, Wu Z, Liu Zh, Huang G (2009) MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. Int Heart J 50:377–387CrossRefGoogle Scholar
  40. 40.
    Okouchi M, Ekshyyan O, Maracine M, Aw TY (2007) Neuronal apoptosis in neurodegeneration. Antioxid Redox Signal 9:1059–1096CrossRefGoogle Scholar
  41. 41.
    Jana A, Hogan EL, Pahan K (2009) Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death. J Neurol Sci 278:5–15CrossRefGoogle Scholar
  42. 42.
    Tang Y, Zheng J, Sun Y, Liu Zh, Huang G (2009) MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. Int Heart J 50(3):377–387CrossRefGoogle Scholar
  43. 43.
    Adair JC, Knoefel JE, Morgan N (2001) Controlled trial of N acetylcysteine for patients with probable Alzheimer’s disease. Neurology 57:1515–1517CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Faculty of Life Sciences and BiotechnologyShahid Beheshti UniversityTehranIran
  2. 2.Department of BiologyIslamic Azad University-Zanjan BranchZanjanIran

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