Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 12, Issue 3, Pages 643-653Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.10.011
Keywords
Chitosan polyplex system; miRNA-124; Microglia/macrophage; Inflammation; Spinal cord injury
Funding
- Swedish Research Council [2014-2306]
- Lundbeck Foundation Nanomedicine Centre for Individualized Management of Tissue Damage and Regeneration (LUNA)
- ERA-Net European transnational collaborative project: Nano-Functionalised Implants for the Regenerative Treatment of Spinal Cord and Nerve Lesions (Nano4Neuro)
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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.
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