Skip to main content Skip to main navigation menu Skip to site footer

miRNA-124 Loaded Chitosan as Novel Therapy to Induce Neuroprotective and Neurogenesis for Improving Brain Revitalization after Ischemic Stroke


Stroke is a world leading cause of death and disability in the field of neurology. Ischemic stroke occurs from the obstruction of blood flow to the brain and accounts for 85% of all strokes. Currently, the initial management of stroke to reduce the mortality rate is well known, resulted in increasing number of stroke survivor over the years.  However, lack of appropriate treatment for post-stroke recovery lead to prolonged disability that will produce a negative impact, in particular for the productive-aged survivor. Researchers found that miRNA-124 has a lot of beneficial effect to the ischemic brain. miRNA-124 will upregulate the growth factor substances and down-regulate the TNF-α and other cytotoxic substances and increase the number of M2 microglia which is important to promote angiogenesis and matrix remodeling. Expression of miRNA-124 will also lead to differentiation and migration of neuro-progenitor cells to the lesion site while reducing the formation of the glial scar. Furthermore, chitosan derived from the extraction of shells, shrimp, and crabs, have been reported for its various advantages such as anti-infection, anti-tumor and also as carrier-mediated transported across blood–brain barrier. Administration of miRNA-124 loaded chitosan by intranasal route will improve the drug delivery into neuron by provides moiety for cell penetration and as affinity agent towards neuronal tissues. Based on those points, the combination of chitosan and miRNA-124 may be a potential therapy to improve revitalization and reduce disability after stroke ischemic.


  1. Mukherjee D patil C. Epidemiology and the Global Burden of Stroke. World Neurosurg. 2011;76(6):85–90. doi:10.1016/j.wneu. 2011.07.023
  2. Palomeras Soler E CR V. Epidemiology and Risk Factor of Cerebral Ischemia and Ischemic Heart Disease: Similarities and Difference. Current Cardiology Reviews. 2010;6(3):138–49.
  3. World Health Organization. Stroke, Cerebrovascular Accident [Internet]. 2014; cited 2015 Jan 17. Available from:
  4. Ghani L ML. DOMINANT RISK FACTORS OF STROKE IN INDONESIA. Buletin Penelitian Kesehatan. 2015;44(1):49–58.
  5. Feigin VL, Mensah GA, Norrving B, et al. GBD 2013 Stroke PaNel Experts Group. Atlas of the Global Burden of Stroke (1990-2013), The GBD 2013 Study. Neuroepidemiology. 2015; 45:230–6.
  6. Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia. Mol Ther - Nucleic Acids [Internet]. 2017;7(June):278–87. Available from: doi:10.1016/j.nano.2015.10.011
  7. Trapani A, De Giglio E, Cafagna D, Denora N, Agrimi G CT et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm. 2011;419(1–2):296–307. doi: 10.1016/j.ijpharm.2011.07.036
  8. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience. 2009;158:1021–9.
  9. Xing C, Arai K, Lo E HM. Pathophysiologic Cascades in Ischemic Stroke. Int J Stroke. 2012;939:1747–4949.
  10. Gutierrez M, Merino JJ, de Lecinana MA, Diez-Tejedor E. Cerebral protection, brain repair, plasticity and cell therapy in ischemic stroke. Cerebrovasc Dis. 2009;27(Supp. 1):177–86.
  11. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10:1387–94.
  12. Kawano H, kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, et al. Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res. 2012;349:169–80. doi:10.1007/s00441-012-1336-5.
  13. Huang L, Wu Z, ZhuGe Q, Zheng W, Shao B WB et al. Glial Scar Formation Occurs in the Human Brain after Ischemic Stroke. Sci Int J Med. 2014;11(4):344–8.
  14. Nowicka D, Rogozinska K, Aleksy M, Witte OW S-KJ. Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain. Acta Neurobiol Exp. 2008;68:68–155.
  15. Louw AM, Kolar MK, Novikova LN, Kingham PJ, Wiberg M, Kjems J, et al. Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury. Nanomedicine Nanotechnology, Biol Med [Internet]. 2016;12(3):643–53. Available from:
  16. Jickling GC, Ander BP, Zhan X, Noblett D, Stamova B, Liu D. microRNA Expression in Peripheral Blood Cells following Acute Ischemic Stroke and Their Predicted Gene Targets. PLoS One. 2014;9(6).
  17. Sun Y, Luo Z-M, Guo X-M, Su D-F, Liu X. An updated role of microRNA-124 in central nervous system disorders: a review. Front Cell Neurosci. 2015;9(May):1–8.
  18. Zhang Yu WZ. Progress in MicroRNA Dlivery. Natl Institutes Heal. 2014;172(3):962–74.
  19. Zhang K, Zhu Y, Liu P, Ji R. MiR-124 inhibits neural apoptosis in ischemic stroke. CNS Neurosci Ther. 2016;9(10):9924–30.
  20. Jakobsson J. Functional studies of microRNAs in neural stem cells : problems and perspectives. Front Neurosci. 2012;6(February):1–10.
  21. Adlakha YK, Saini N. Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128. Mol Cancer. 2014;13(1):1–18.
  22. Pillai C, Paul W, Sharma C. R. Chitin and chitosan polymers: Chemistry, solubility and fiber formation. Prog Polym Sci. 2009;34(7):641–78. doi:10.1016/j.progpolymsci.2009.04.001.
  23. Du Y, Ding y, Sun m, Zhang l, Jiang X, Yang C. Hollow chitosan/ poly(acrylic acid) nanospheres as drug carriers. Biomacromolecules. 2007;8:1069-76.
  24. Dash M, Chiellini F, Ottenbrite R, Chiellini E. A versatile semi-synthetic polymer in biomedical applications. Progress in Polymer Science. 2011;36(8):981–1014.
  25. Yu Y, Luo T, Liu S, Song G, Han J WY et al. Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice. J Atheroscler Thromb. 2015;22(9):926–41.
  26. Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics. 2012;81(3):463–69. doi:10.1016/j.ejpb.2012.04.007.
  27. Malhotra M, Tomaro-Duchesneau C, Saha S, Prakash S. Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles. J Pharm [Internet]. 2013;2013:1–
  28. Available from: doi:10.1155/2013/812387
  29. Rong S, Zhang J. Modulatory role of microRNA-124 in targeting Ku70 during post-stroke neuronal apoptosis. Int J Clin Exp Pathol. 2017;10(3):3697–702.
  30. Guo YE, Steitz JA. 3 ′ -Biotin-tagged microRNA-27 does not associate with Argonaute proteins in cells. RNA Journal. 2014;20:985–8.
  31. Parvathi M. Intranasal Drug Delivery To Brain: an Overview. Int J Res Pharm Chem. 2012;2(3):889–95.
  32. Sun Y, Gui H, Li Q, Luo ZM, Zheng MJ, Duan JL, et al. MicroRNA-124 protects neurons against apoptosis in cerebral ischemic stroke. CNS Neurosci Ther. 2013;19(10):813–9.
  33. Hamzei Taj S, Kho W, Riou A, Wiedermann D, Hoehn M. MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia. Biomaterials. 2016;91:151–65.
  34. Akhtar RS, Ness JM, Roth KA. Bcl-2 family regulation of neuronal development and neurodegeneration. Biochim Biophys Acta - Mol Cell Res [Internet]. 2008;1644(2–3):189–203. Available from:
  35. Broughton BRS, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke. 2009;40(5).
  36. Khoshnam SE, Winlow W, Farbood Y, Moghaddam F. Emerging Roles of microRNAs in Ischemic Stroke : As Possible Therapeutic Agents. Journal of Stroke. 2017;1–22. doi:10.5853/jos.2016.01368.
  37. Gao Z, Zhu Q, Zhang Y, Zhao Y, Cai L, Shields CB, et al. Reciprocal modulation between microglia and astrocyte in reactive gliosis following the CNS injury. Mol Neurobiol. 2013;48(3):690–701.
  38. Vong KI, Leung CKY, Behringer RR, Kwan KM. Sox9 is critical for suppression of neurogenesis but not initiation of gliogenesis in the cerebellum. Mol Brain [Internet]. 2015;8(1):25. Available from:
  39. Sun AX, Crabtree GR, Yoo AS. MicroRNAs: Regulators of neuronal fate. Curr Opin Cell Biol. 2013;25(2):215–21.
  40. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev
  41. Neurosci [Internet]. 2004;5(2):146–56. Available from: doi:10.1038/nrn1326.
  42. Nagpal K, Singh SK, Mishra DN. Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety. Int J Biol Macromol [Internet]. 2013;59:72–83. Available from:

How to Cite

Maliawan, R. P., Veronica, S., Arista Dewi, N. P. A. P., Wisnu Arya Wardana, P., Wisnu Wardhana, D. P., & Maliawan, S. (2018). miRNA-124 Loaded Chitosan as Novel Therapy to Induce Neuroprotective and Neurogenesis for Improving Brain Revitalization after Ischemic Stroke. Bali Medical Journal, 7(2).




Search Panel

Rataya Paramitha Maliawan
Google Scholar
BMJ Journal

Sieny Veronica
Google Scholar
BMJ Journal

Ni Putu Ayu Pande Arista Dewi
Google Scholar
BMJ Journal

Putu Wisnu Arya Wardana
Google Scholar
BMJ Journal

Dewa Putu Wisnu Wardhana
Google Scholar
BMJ Journal

Sri Maliawan
Google Scholar
BMJ Journal