Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (10): 1687-1694.doi: 10.4103/1673-5374.217348

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Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates motor function recovery after spinal cord injury

Yue-min Ding1, Yu-ying Li2, Chu Wang1, Hao Huang1, Chen-chen Zheng1, Shao-han Huang1, Yang Xuan1, Xiao-yi Sun3, Xiong Zhang4   

  1. 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
  • Received:2017-08-20 Online:2017-10-15 Published:2017-10-15
  • Contact: Xiong Zhang, Ph.D. or Xiao-yi Sun, Ph.D.,xiongzhang@zju.edu.cn or sunxiaoyi@zucc.edu.cn.
  • Supported by:

    This work was supported by the Natural Science Foundation of Zhejiang Province of China, No. LY15H250001 and LY14H090002;the National Natural Science Foundation of China, No. 81000535 and 81402872; the Medical Science and Technology Project Foundation of Zhejiang Province of China, No. 2014KYA166; and the Science and Technology Innovation Talents Development Plan Foundation for High School Students in Zhejiang Province of China, No. 2014R401186.

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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 (PEIALG) 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-siRNA 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 nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

Key words: nerve regeneration, spinal cord injury, polyethylenimine, alginate, nanoparticles, nischarin, small interfering RNA, necrotic area, growth-associated protein-43, motor function, neural regeneration