Chitosan polyplex mediated delivery of miRNA-124 reduces activation of microglial cells in vitro and in rat models of spinal cord injury
2016 (English)In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 12, no 3, 643-653 p.Article in journal (Refereed) Published
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 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.
Place, publisher, year, edition, pages
2016. Vol. 12, no 3, 643-653 p.
Basic Medicine Nano Technology
Research subject Human Anatomy
IdentifiersURN: urn:nbn:se:umu:diva-117111DOI: 10.1016/j.nano.2015.10.011ISI: 000373924000007PubMedID: 26582736OAI: oai:DiVA.org:umu-117111DiVA: diva2:905241
2016-05-16: Originally published in manuscript form.2016-02-222016-02-222016-06-08Bibliographically approved