Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection
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. I...
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Frontiers Media S.A.
2017-11-01
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Series: | Frontiers in Cellular Neuroscience |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00381/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing Li Jing Li Shuangxi Chen Zhikai Zhao Yunhao Luo Yuhui Hou Heng Li Liumin He Libing Zhou Wutian Wu Wutian Wu Wutian Wu |
spellingShingle |
Jing Li Jing Li Shuangxi Chen Zhikai Zhao Yunhao Luo Yuhui Hou Heng Li Liumin He Libing Zhou Wutian Wu Wutian Wu Wutian Wu Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection Frontiers in Cellular Neuroscience spinal cord transection locomotor function vascular endothelial growth factor MAPK signaling neural circuitry |
author_facet |
Jing Li Jing Li Shuangxi Chen Zhikai Zhao Yunhao Luo Yuhui Hou Heng Li Liumin He Libing Zhou Wutian Wu Wutian Wu Wutian Wu |
author_sort |
Jing Li |
title |
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection |
title_short |
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection |
title_full |
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection |
title_fullStr |
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection |
title_full_unstemmed |
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection |
title_sort |
effect of vegf on inflammatory regulation, neural survival, and functional improvement in rats following a complete spinal cord transection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2017-11-01 |
description |
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. |
topic |
spinal cord transection locomotor function vascular endothelial growth factor MAPK signaling neural circuitry |
url |
http://journal.frontiersin.org/article/10.3389/fncel.2017.00381/full |
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doaj-7f26b76c6677492f8ee99ba3d10847622020-11-24T22:27:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-11-011110.3389/fncel.2017.00381295691Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord TransectionJing Li0Jing Li1Shuangxi Chen2Zhikai Zhao3Yunhao Luo4Yuhui Hou5Heng Li6Liumin He7Libing Zhou8Wutian Wu9Wutian Wu10Wutian Wu11Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaDepartment of Anatomy, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaDepartment of Anatomy, University of Hong Kong, Hong Kong, Hong KongKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, ChinaDepartment of Anatomy, University of Hong Kong, Hong Kong, Hong KongRe-Stem Biotechnology Co., Ltd., Suzhou, ChinaAfter 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.http://journal.frontiersin.org/article/10.3389/fncel.2017.00381/fullspinal cord transectionlocomotor functionvascular endothelial growth factorMAPK signalingneural circuitry |