title: Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury.
abstract: 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-α 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 72 h 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.
  
  
  BACKGROUND
  The treatment of spinal cord injury remains an unresolved problem. Secondary damage is often the result of inflammation caused by activated microglia and/or macrophages. In this article, the authors developed their formulation of chitosan/miR-124 polyplex particles and investigated their use in the suppression of neuronal inflammation. This exciting data may provide a new horizon for patients who suffer from spinal cord injury.
authors.affiliation: Interdisciplinary Nanoscience Center, Aarhus University, Aarhus C., Denmark.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Louw
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Mallappa K
authors.initials: MK
authors.lastname: Kolar
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Liudmila N
authors.initials: LN
authors.lastname: Novikova
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
authors.affiliation: Interdisciplinary Nanoscience Center, Aarhus University, Aarhus C., Denmark. Electronic address: jk@mbg.au.dk.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden. Electronic address: lev.novikov@umu.se.
authors.forename: Lev N
authors.initials: LN
authors.lastname: Novikov
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D035683:MicroRNAs / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014162:Transfection
chemical_list: C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; D048271:Chitosan
keywords: Chitosan polyplex system; Inflammation; Microglia/macrophage; Spinal cord injury; miRNA-124