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Front. Cell. Neurosci. | doi: 10.3389/fncel.2017.00381

Effect of VEGF on inflammatory regulation, neural survival and functional improvement in rats following a complete spinal cord transection

 Jing Li1,  Shuangxi Chen1, Zhikai Zhao1, Yunhao Luo1, Yuhui Hou1, Heng Li2, Liumin He3, Libing Zhou1 and  Wutian Wu2*
  • 1Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, China
  • 2The Chinese University of Hong Kong, Hong Kong
  • 3Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, China

After complete transection of the thoracic spinal segment, neonatal rats exhibit spontaneous locomotor recovery of hindlimbs, but this recovery is not found in adult rats after similar injury. The potential mechanism related to the difference in recovery of neonatal and adult rats remains unknown. In this study, 342 animals were analyzed. The vascular endothelial growth factor (VEGF) level in spinal segments below injury sites was significantly higher in postnatal day 1 rats (P1) compared with 28-day-old adult rats (P28) following a complete T9 transection. VEGF administration in P28 rats with T9 transection significantly improved the functional recovery; by contrast, treatment with VEGF receptor inhibitors in P1 rats with T9 transection slowed down the spontaneous functional recovery. Results showed more neurons reduced in the lumbar spinal cord and worse local neural network reorganization below injury sites in P28 rats than those in P1 rats. Transynaptic tracing with pseudorabies virus and double immunofluorescence analysis indicated that VEGF treatment in P28 rats alleviated the reduced number of neurons and improved their network reorganization. VEGF inhibition in neonates resulted in high neuronal death rate and deteriorated network reorganization. In in vivo studies, T9 transection induced less increase in the number of microglia in the spinal cord in P1 animals than P28 animals. VEGF treatment reduced the increase in microglial cells in P28 animals. VEGF administration in cultured spinal motoneurons prevented lipopolysaccharide (LPS)-induced neuronal death and facilitated neurite growth. Western blots of the samples of lumbar spinal cord after spinal transection and cultured spinal motoneurons showed a lower level of Erk1/2 phosphorylation after the injury or LPS induction compared with that in the control. The phosphorylation level increased after VEGF treatment. In conclusion, VEGF is a critical mediator involved in functional recovery after spinal transection and can be considered a potential target for clinical therapy.

Keywords: spinal cord transection, Locomotor function, Vascular Endothelial Growth Factor, MAPK signaling, neural circuitry

Received: 17 Jul 2017; Accepted: 14 Nov 2017.

Edited by:

Chao Deng, University of Wollongong, Australia

Reviewed by:

Catherine Gorrie, University of Technology Sydney, Australia
Albert Rizvanov, Kazan Federal University, Russia  

Copyright: © 2017 Li, Chen, Zhao, Luo, Hou, Li, He, Zhou and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Wutian Wu, The Chinese University of Hong Kong, Hong Kong, Hong Kong, wtwu@hku.hk