scholarly journals Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

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 between adjacent endothelial cells, including tight junctions (TJ) and adhesion junctions (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 delayed recovery after SCI. We introduced water treadmill training (TT) for the first time, which can help SCI rats successfully exercise and measured the effect of TT in promoting recovery after SCI and possible mechanisms involved.Methods: Sprague-Dawley (200–250g) rats were randomly divided into three groups: Sham operated, SCI, and SCI + TT. Animals were sacrificed 7 d or 14 d post-surgery. The degree of neurological deficit as assessed by the Basso-Beattie-Bresnahan motor rating scale, tissue water content, BSCB permeability, apoptosis, protein expression and ultrastructure of vascular endothelial cells were assessed, Western blot, immunofluorescence and transmission electron microscopy. Results: Our experiments showed that TT reduced the permeability of BSCB and decreased tissue structural damage. TT improved functional recovery significantly when compared with the SCI group; TJ and AJ proteins expression increased significantly after TT training and training reduced apoptosis induced by SCI. TT can promote angiogenesis and the expression of MMP-2 and MMP-9 was significantly inhibited by TT.Conclusions: In this study, the results indicate that TT promotes functional recovery 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.

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.


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.


2017 ◽  
Vol 55 (3) ◽  
pp. 2577-2590 ◽  
Author(s):  
Hemant Kumar ◽  
Min-Jae Jo ◽  
Hyemin Choi ◽  
Manjunatha S. Muttigi ◽  
Seil Shon ◽  
...  

Neurosurgery ◽  
2014 ◽  
Vol 75 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jing Tong ◽  
Yi Ren ◽  
Xiaowei Wang ◽  
Vassilios G. Dimopoulos ◽  
Henry N. Kesler ◽  
...  

Abstract BACKGROUND: Neuronal Nogo-66 receptor 1 (NgR1) has attracted attention as a converging point for mediating the effects of myelin-associate inhibitory ligands in the central nervous system, establishing the growth-restrictive environment, and limiting axon regeneration after traumatic injury. OBJECTIVE: To investigate the factors that may be contributing to the discrepancy in the importance of NgR1, which has been undermined by several studies that have shown the lack of substantial axon regeneration after spinal cord injury (SCI) in NgR1-knockout or -knockdown animal models. METHODS: We used mice carrying either a homozygous or heterozygous null mutation in the NgR1 gene and subjected them to either a moderate or severe SCI. RESULTS: Locomotor function assessments revealed that the level of functional recovery is affected by the degree of injury suffered. NgR1 ablation enhanced local collateral sprouting in the mutant mice. Reactive astrocytes and chondroitin sulfate proteoglycans (CSPGs) are upregulated surrounding the injury site. Matrix metalloproteinase-9, which has been shown to degrade CSPGs, was significantly upregulated in the homozygous mutant mice compared with the heterozygous or wild-type mice. However, CSPG levels remained higher in the homozygous compared with the heterozygous mice, suggesting that CSPG-degrading activity of matrix metalloproteinase-9 may require the presence of NgR1. CONCLUSION: Genetic ablation of NgR1 may lead to significant recovery in locomotor function after SCI. The difference in locomotor recovery we observed between the groups that suffered various degrees of injury suggests that injury severity may be a confounding factor in functional recovery after SCI.


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