Frontiers in Neuroscience (Apr 2022)
The Overexpression of Insulin-Like Growth Factor-1 and Neurotrophin-3 Promote Functional Recovery and Alleviate Spasticity After Spinal Cord Injury
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Zuliyaer Talifu,
- Chuan Qin,
- Zhang Xin,
- Yixin Chen,
- Yixin Chen,
- Yixin Chen,
- Yixin Chen,
- Yixin Chen,
- Yixin Chen,
- Jiayi Liu,
- Jiayi Liu,
- Jiayi Liu,
- Jiayi Liu,
- Jiayi Liu,
- Subarna Dangol,
- Subarna Dangol,
- Subarna Dangol,
- Subarna Dangol,
- Subarna Dangol,
- Xiaodong Ma,
- Xiaodong Ma,
- Xiaodong Ma,
- Xiaodong Ma,
- Xiaodong Ma,
- Han Gong,
- Han Gong,
- Han Gong,
- Han Gong,
- Han Gong,
- Zhisheng Pei,
- Zhisheng Pei,
- Zhisheng Pei,
- Yan Yu,
- Yan Yu,
- Yan Yu,
- Yan Yu,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Jianjun Li,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du,
- Liangjie Du
Affiliations
- Zuliyaer Talifu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Zuliyaer Talifu
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Zuliyaer Talifu
- Chinese Institute of Rehabilitation Science, Beijing, China
- Zuliyaer Talifu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Zuliyaer Talifu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Zuliyaer Talifu
- School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, China
- Chuan Qin
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Zhang Xin
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
- Yixin Chen
- School of Rehabilitation, Capital Medical University, Beijing, China
- Yixin Chen
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Yixin Chen
- Chinese Institute of Rehabilitation Science, Beijing, China
- Yixin Chen
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Yixin Chen
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Yixin Chen
- Department of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha, China
- Jiayi Liu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Jiayi Liu
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Jiayi Liu
- Chinese Institute of Rehabilitation Science, Beijing, China
- Jiayi Liu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Jiayi Liu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Subarna Dangol
- School of Rehabilitation, Capital Medical University, Beijing, China
- Subarna Dangol
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Subarna Dangol
- Chinese Institute of Rehabilitation Science, Beijing, China
- Subarna Dangol
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Subarna Dangol
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Xiaodong Ma
- School of Rehabilitation, Capital Medical University, Beijing, China
- Xiaodong Ma
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Xiaodong Ma
- Chinese Institute of Rehabilitation Science, Beijing, China
- Xiaodong Ma
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Xiaodong Ma
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Han Gong
- School of Rehabilitation, Capital Medical University, Beijing, China
- Han Gong
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Han Gong
- Chinese Institute of Rehabilitation Science, Beijing, China
- Han Gong
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Han Gong
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Zhisheng Pei
- Chinese Institute of Rehabilitation Science, Beijing, China
- Zhisheng Pei
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Zhisheng Pei
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Yan Yu
- School of Rehabilitation, Capital Medical University, Beijing, China
- Yan Yu
- Chinese Institute of Rehabilitation Science, Beijing, China
- Yan Yu
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Yan Yu
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Jianjun Li
- School of Rehabilitation, Capital Medical University, Beijing, China
- Jianjun Li
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Jianjun Li
- Chinese Institute of Rehabilitation Science, Beijing, China
- Jianjun Li
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Jianjun Li
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- Jianjun Li
- School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, China
- Liangjie Du
- School of Rehabilitation, Capital Medical University, Beijing, China
- Liangjie Du
- Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China
- Liangjie Du
- Chinese Institute of Rehabilitation Science, Beijing, China
- Liangjie Du
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- Liangjie Du
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
- DOI
- https://doi.org/10.3389/fnins.2022.863793
- Journal volume & issue
-
Vol. 16
Abstract
ObjectiveThis study was conducted to investigate the effects of the exogenous overexpression of nerve growth factors NT-3 and IGF-1 on the recovery of nerve function after spinal cord injury (SCI) and identify the potential mechanism involved.MethodsSixty-four female SD rats were randomly divided into four groups: an SCI group, an adeno-associated viral (AAV)-RFP and AAV-GFP injection group, an AAV-IGF-1 and AAV-NT-3 injection group, and a Sham group. After grouping, the rats were subjected to a 10-week electrophysiological and behavioral evaluation to comprehensively evaluate the effects of the intervention on motor function, spasticity, mechanical pain, and thermal pain. Ten weeks later, samples were taken for immunofluorescence (IF) staining and Western blot (WB) detection, focusing on the expression of KCC2, 5-HT2A, and 5-HT2C receptors in motor neurons and the spinal cord.ResultsElectrophysiological and behavioral data indicated that the AAV-IGF-1 and AAV-NT-3 groups showed better recovery of motor function (P < 0.05 from D14 compared with the AAV-RFP + AAV-GFP group; P < 0.05 from D42 compared with SCI group) and less spasticity (4–10 weeks, at 5 Hz all P < 0.05 compared with SCI group and AAV- RFP + AAV-GFP group) but with a trend for more pain sensitivity. Compared with the SCI group, the von Frey value result of the AAV-IGF-1 and AAV-NT-3 groups showed a lower pain threshold (P < 0.05 at 4–8 weeks), and shorter thermal pain threshold (P < 0.05 at 8–10 weeks). IF staining further suggested that compared with the SCI group, the overexpression of NT-3 and IGF-1 in the SCI-R + G group led to increased levels of KCC2 (p < 0.05), 5-HT2A (p < 0.05), and 5-HT2C (p < 0.001) in motor neurons. WB results showed that compared with the SCI group, the SCI-R + G group exhibited higher expression levels of CHAT (p < 0.01), 5-HT2A (p < 0.05), and 5-HT2C (p < 0.05) proteins in the L2-L6 lumbar enlargement.ConclusionData analysis showed that the overexpression of NT-3 and IGF-1 may improve motor function after SCI and alleviate spasms in a rat model; however, these animals were more sensitive to mechanical pain and thermal pain. These behavioral changes may be related to increased numbers of KCC2, 5-HT2A, and 5-HT2C receptors in the spinal cord tissue. The results of this study may provide a new theoretical basis for the clinical treatment of SCI.
Keywords
