X Li1, D Pan2. 1. Department of Spinal Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, China. 2. Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, China.
Abstract
OBJECTIVE: To investigate the effect of transforming growth factor (TGF-β) inhibition on functional recovery of spinal cord injury in mice. METHODS: Twelve mice were divided into treatment group, control group and sham-operated group (n=4). The mice in the treatment group were subjected to hemisection of the spinal cord and received intraperitoneal injection of TGF-β neutralizing antibody (1D11) 3 times a week (25 μL each time), and those in control group were injected with the vehicle antibody (13C4) following spinal cord hemisection. The sham-operated mice underwent sham operation to expose the spinal cord without hemisection. Four weeks later, the heart of the mice was perfused and 1-2 cm of the spinal cord spanning the injury site was harvested. Immunofluorescence staining of FSP1, fibronectin, and PGP9.5 was performed to assess fibroblast recruitment in the injury area, fibronectin deposition, and neurological recovery. For further verification of the results, we used a mouse model of spinal cord clamp injury to observe the survival of axons and distribution of astrocytes by detecting expressions of 5-HT and GFAP with immunofluorescence assay. RESULTS: In the hemisection injury model, fibroblasts recruitment and fibronectin deposition in the injured area was significantly reduced and the neurological function was improved in 1D11 treatment group as compared with those in 13C4-treated group (P < 0.05). In the spinal cord clamp injury model, treatment with 1D11, as compared with the 13C4, resulted in significantly increased number of 5-HT-positive axons with extended axonal length and obviously increased the number of GFAP-positive astrocytes in the injured area (P < 0.05). CONCLUSION: Inhibiting TGF-β after spinal cord injury can reduce the recruitment of fibroblasts and fibronectin deposition to promote recovery of neurological function and repair of the injured spinal cord in mice.
OBJECTIVE: To investigate the effect of transforming growth factor (TGF-β) inhibition on functional recovery of spinal cord injury in mice. METHODS: Twelve mice were divided into treatment group, control group and sham-operated group (n=4). The mice in the treatment group were subjected to hemisection of the spinal cord and received intraperitoneal injection of TGF-β neutralizing antibody (1D11) 3 times a week (25 μL each time), and those in control group were injected with the vehicle antibody (13C4) following spinal cord hemisection. The sham-operated mice underwent sham operation to expose the spinal cord without hemisection. Four weeks later, the heart of the mice was perfused and 1-2 cm of the spinal cord spanning the injury site was harvested. Immunofluorescence staining of FSP1, fibronectin, and PGP9.5 was performed to assess fibroblast recruitment in the injury area, fibronectin deposition, and neurological recovery. For further verification of the results, we used a mouse model of spinal cord clamp injury to observe the survival of axons and distribution of astrocytes by detecting expressions of 5-HT and GFAP with immunofluorescence assay. RESULTS: In the hemisection injury model, fibroblasts recruitment and fibronectin deposition in the injured area was significantly reduced and the neurological function was improved in 1D11 treatment group as compared with those in 13C4-treated group (P < 0.05). In the spinal cord clamp injury model, treatment with 1D11, as compared with the 13C4, resulted in significantly increased number of 5-HT-positive axons with extended axonal length and obviously increased the number of GFAP-positive astrocytes in the injured area (P < 0.05). CONCLUSION: Inhibiting TGF-β after spinal cord injury can reduce the recruitment of fibroblasts and fibronectin deposition to promote recovery of neurological function and repair of the injured spinal cord in mice.
Authors: Greg M Harris; Nicolas N Madigan; Karen Z Lancaster; Lynn W Enquist; Anthony J Windebank; Jeffrey Schwartz; Jean E Schwarzbauer Journal: Matrix Biol Date: 2016-09-15 Impact factor: 11.583
Authors: Laura E Clarke; Gordon X Wang; Won-Suk Chung; Benjamin K Stafford; Alexander Sher; Chandrani Chakraborty; Julia Joung; Lynette C Foo; Andrew Thompson; Chinfei Chen; Stephen J Smith; Ben A Barres Journal: Nature Date: 2013-11-24 Impact factor: 49.962