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Application of the sodium hyaluronate-CNTF scaffolds in repairing adult rat spinal cord injury and facilitating neural network formation

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Abstract

The present study aimed to explore the potential of the sodium hyaluronate-CNTF (ciliary neurotrophic factor) scaffold in activating endogenous neurogenesis and facilitating neural network re-formation after the adult rat spinal cord injury (SCI). After completely cutting and removing a 5-mm adult rat T8 segment, a sodium hyaluronate-CNTF scaffold was implanted into the lesion area. Dil tracing and immunofluorescence staining were used to observe the proliferation, differentiation and integration of neural stem cells (NSCs) after SCI. A planar multielectrode dish system (MED64) was used to test the electrophysiological characteristics of the regenerated neural network in the lesioned area. Electrophysiology and behavior evaluation were used to evaluate functional recovery of paraplegic rat hindlimbs. The Dil tracing and immunofluorescence results suggest that the sodium hyaluronate-CNTF scaffold could activate the NSCs originating from the spinal cord ependymal, and facilitate their migration to the lesion area and differentiation into mature neurons, which were capable of forming synaptic contact and receiving glutamatergic excitatory synaptic input. The MED64 results suggest that functional synapsis could be established among regenerated neurons as well as between regenerated neurons and the host tissue, which has been evidenced to be glutamatergic excitatory synapsis. The electrophysiology and behavior evaluation results indicate that the paraplegic rats’ sensory and motor functions were recovered in some degree. Collectively, this study may shed light on paraplegia treatment in clinics.

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Acknowledgements

This work was supported by the State Key Program of the National Natural Science Foundation of China (31130022, 31320103903, 31271037 & 31670988), the International Cooperation in Science and Technology Project of the Ministry of Science and Technology of China (2014DFA30640), the National Ministry of Education Special Fund for Excellent Doctoral Dissertation (201356), the Special Fund for Excellent Doctoral Dissertation of Beijing (20111000601), and the Special Funds for Beijing Base Construction & Talent Cultivation (171100002217066).

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Authors and Affiliations

  1. Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China

    Yabin Xie, Wen Zhao, Yudan Gao, Junkui Shang, Peng Hao, Zhaoyang Yang, Hongmei Duan & Xiaoguang Li

  2. School of Rehabilitation Medicine, China Rehabilitation Research Centre, Capital Medical University, Beijing, 100069, China

    Wei Song

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  1. Yabin Xie
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  2. Wei Song
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  3. Wen Zhao
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  4. Yudan Gao
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  5. Junkui Shang
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  6. Peng Hao
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  7. Zhaoyang Yang
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  8. Hongmei Duan
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  9. Xiaoguang Li
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Correspondence to Zhaoyang Yang, Hongmei Duan or Xiaoguang Li.

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Xie, Y., Song, W., Zhao, W. et al. Application of the sodium hyaluronate-CNTF scaffolds in repairing adult rat spinal cord injury and facilitating neural network formation. Sci. China Life Sci. 61, 559–568 (2018). https://doi.org/10.1007/s11427-017-9217-2

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  • DOI: https://doi.org/10.1007/s11427-017-9217-2

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