Application of the sodium hyaluronate-CNTF scaffolds in repairing adult rat spinal cord injury and facilitating neural network formation
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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.
Keywordsspinal cord injury endogenous neural stem cells neural network reconstruction CNTF new born neuron
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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).
- Luo, Y., Coskun, V., Liang, A., Yu, J., Cheng, L., Ge, W., Shi, Z., Zhang, K., Li, C., Cui, Y., Lin, H., Luo, D., Wang, J., Lin, C., Dai, Z., Zhu, H., Zhang, J., Liu, J., Liu, H., de Vellis, J., Horvath, S., Sun, Y.E., and Li, S. (2015). Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells. Cell 161, 1175–1186.CrossRefPubMedPubMedCentralGoogle Scholar
- Martin Bauknight, W., Chakrabarty, S., Hwang, B.Y., Malone, H.R., Joshi, S., Bruce, J.N., Sander Connolly, E., Winfree, C.J., Cunningham, M.G., Martin, J.H., and Haque, R. (2012). Convection enhanced drug delivery of BDNF through a microcannula in a rodent model to strengthen connectivity of a peripheral motor nerve bridge model to bypass spinal cord injury. J Clin Neurosci 19, 563–569.CrossRefPubMedGoogle Scholar
- Mladinic, M., and Nistri, A. (2013). Microelectrode arrays in combination with in vitro models of spinal cord injury as tools to investigate pathological changes in network activity: facts and promises. Front Neuroeng 3, 1–7.Google Scholar
- Tuinstra, H.M., Aviles, M.O., Shin, S., Holland, S.J., Zelivyanskaya, M.L., Fast, A.G., Ko, S.Y., Margul, D.J., Bartels, A.K., Boehler, R.M., Cummings, B.J., Anderson, A.J., and Shea, L.D. (2012). Multifunctional, multichannel bridges that deliver neurotrophin encoding lentivirus for regeneration following spinal cord injury. Biomaterials 33, 1618–1626.CrossRefPubMedGoogle Scholar