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Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates motor function recovery after spinal cord injury
Authors:Yue-min Ding  Yu-ying Li  Chu Wang  Hao Huang  Chen-chen Zheng  Shao-han Huang  Yang Xuan  Xiao-yi Sun  Xiong Zhang
Affiliation:1. Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang Province, China;2. Department of Physiology, School of Medicine, Quzhou College of Technology, Quzhou, Zhejiang Province, China;3. Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang Province, China;4. Department of Basic Medicine, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
Abstract:A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siR-NA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanopar-ticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.
Keywords:nerve regeneration  spinal cord injury  polyethylenimine  alginate  nanoparticles  nischarin  small interfering RNA  necrotic area  growth-associated protein-43  motor function  neural regeneration
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