Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury

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  • Andrew M. Louw
  • ,
  • Mallappa K. Kolar, Umeå University
  • ,
  • Liudmila N. Novikova, Umeå University
  • ,
  • Paul J. Kingham, Umeå University
  • ,
  • Mikael Wiberg, Umeå University
  • ,
  • Jorgen Kjems
  • Lev N. Novikov, Umeå University

Traumatic injury to the central nervous system (CNS) is further complicated by an increase in secondary neuronal damage imposed by activated microglia/macrophages. MicroRNA-124 (miR-124) is responsible for mouse monocyte quiescence and reduction of their inflammatory cytokine production. We describe the formulation and ex vivo transfection of chitosan/miR-124 polyplex particles into rat microglia and the resulting reduction of reactive oxygen species (ROS) and TNF-alpha and lower expression of MHC-II. Upon microinjection into uninjured rat spinal cords, particles formed with Cy3-labeled control sequence RNA, were specifically internalized by OX42 positive macrophages and microglia cells. Alternatively particles injected in the peritoneum were transported by macrophages to the site of spinal cord injury 72h post injection. Microinjections of chitosan/miR-124 particles significantly reduced the number of ED-1 positive macrophages in the injured spinal cord. Taken together, these data present a potential treatment technique to reduce inflammation for a multitude of CNS neurodegenerative conditions. (C) 2015 The Authors. Published by Elsevier Inc.

Original languageEnglish
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume12
Issue3
Pages (from-to)643-653
Number of pages11
ISSN1549-9634
DOIs
Publication statusPublished - Apr 2016

    Research areas

  • Chitosan polyplex system, miRNA-124, Microglia/macrophage, Inflammation, Spinal cord injury, TRAUMATIC BRAIN-INJURY, PARKINSONS-DISEASE, MULTIPLE-SCLEROSIS, SUBSTANTIA-NIGRA, GLIAL SCAR, MACROPHAGE, NANOPARTICLES, ALPHA, CNS, DIFFERENTIATION

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