Vascular Regeneration Therapies for Spinal Cord Injury

Author(s):  
Naosuke Kamei
2019 ◽  
Vol 27 (12) ◽  
pp. 2134-2146 ◽  
Author(s):  
Shuangfei Ni ◽  
Zixiang Luo ◽  
Liyuan Jiang ◽  
Zhu Guo ◽  
Ping Li ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  

Abstract Background The permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis. The failure of new blood vessels to effectively regenerate is also an important cause of delayed recovery after SCI. For the first time, we introduced water treadmill training (TT) to help SCI rats successfully exercise and measured the effects of TT in promoting recovery after SCI and the possible mechanisms involved. Methods Sprague-Dawley (200–250 g) rats were randomly divided into the following three groups: sham operated, SCI, and SCI + TT. Animals were sacrificed at 7 or 14 days post-surgery. The degree of neurological deficit, tissue morphology and BSCB permeability were assessed by the Basso-Beattie-Bresnahan (BBB) motor function scale and appropriate staining protocols, and apoptosis, protein expression and vascular EC ultrastructure were assessed by TUNEL staining, Western blotting, immunofluorescence and transmission electron microscopy (TEM). Results Our experiments showed that TT reduced permeability of the BSCB and decreased structural tissue damage. TT significantly improved functional recovery when compared with that in the SCI group; TJ and AJ proteins expression increased significantly after TT, and training reduced apoptosis induced by SCI. TT could promote angiogenesis, and MMP-2 and MMP-9 expression was significantly inhibited by TT. Conclusions The results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage.


2020 ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  

Abstract Background: The permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis. The failure of new blood vessels to effectively regenerate is also an important cause of delayed recovery after SCI. For the first time, we introduced water treadmill training (TT) to help SCI rats successfully exercise and measured the effects of TT in promoting recovery after SCI and the possible mechanisms involved.Methods: Sprague-Dawley (200–250g) rats were randomly divided into the following three groups: sham operated, SCI, and SCI + TT. Animals were sacrificed at 7 or 14 d post-surgery. The degree of neurological deficit, tissue morphology and BSCB permeability were assessed by the Basso-Beattie-Bresnahan (BBB) motor function scale and appropriate staining protocols, and apoptosis, protein expression and vascular EC ultrastructure were assessed by TUNEL staining, Western blotting, immunofluorescence and transmission electron microscopy (TEM).Results: Our experiments showed that TT reduced permeability of the BSCB and decreased structural tissue damage. TT significantly improved functional recovery when compared with that in the SCI group; TJ and AJ proteins expression increased significantly after TT, and training reduced apoptosis induced by SCI. TT could promote angiogenesis, and MMP-2 and MMP-9 expression was significantly inhibited by TT.Conclusions: The results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage.


2020 ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  

Abstract Background: The permeability of blood-spinal cord barrier (BSCB) is mainly determined by the junction complex of adjacent endothelial cells, including tight junction (TJ) and adhesion junction (AJ), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinase (MMP) leads to inflammation, neurotoxin production, and apoptosis of neurons. The failure of effective regeneration of new blood vessels is also an important reason for the difficulty of recovery after SCI. We introduced water treadmill training (TT) for the first time, which can help SCI rats successfully exercise, and we explored the role of TT in promoting the ability to exercise after SCI and its possible mechanism.Methods: Sprague-Dawley (200–250g) rats were randomly divided into three groups. SCI models were established and rats underwent TT after SCI. Animals were sacrificed 7 d or 14 d post-surgery. The degree of neurological deficit, water content, BSCB permeability, apoptosis, protein expression and ultrastructure of vascular endothelial cells (EC) were assessed by the Basso-Beattie-Bresnahan (BBB) motor rating scale, haematoxylin-eosin (HE) staining, Evans blue (EB) staining, TUNEL staining, Western blot (WB) experiments, and immunofluorescence and transmission electron microscopy (TEM). Results: Our experiments show that TT reduces the permeability of BSCB and decreased tissue structure damage. TT improved functional recovery and it has significant significance when compared with the M group after SCI; TJ and AJ proteins increased significantly after TT training in SCI rats. TT training reduced apoptosis induced by SCI. TT can promote angiogenesis and the expressions of MMP-2 and MMP-9 were significantly inhabited by TT after SCI.Conclusions: In this study, the results indicate that TT promotes functional recovery partly for the following reasons: (1) TT protects residual BSCB structure from further damage; (2) it promotes vascular regeneration; and (3) it inhibits the expression of MMP-2/9 to mitigate BSCB damage.


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