scholarly journals Water treadmill training protects the integrity of the blood-spinal cord barrier following SCI via the BDNF/TrkB-CREB signalling pathway

2021 ◽  
Vol 143 ◽  
pp. 104945
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Xiaolan Yu ◽  
Shengcun Li ◽  
Qiaoyun Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treadmill Training ◽  
Signalling Pathway ◽  
Blood Spinal Cord Barrier ◽  
Water Treadmill

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 ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Functional Recovery ◽  
Treadmill Training ◽  
Apoptosis Protein ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Water Treadmill

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.

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 ◽  
Vol 17 (1) ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Treadmill Training ◽  
Vascular Regeneration ◽  
Post Surgery ◽  
Apoptosis Protein ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Water Treadmill

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.

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 ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Treadmill Training ◽  
Vascular Regeneration ◽  
Post Surgery ◽  
Apoptosis Protein ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Water Treadmill

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.

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

2020 ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endothelial Cells ◽  
Functional Recovery ◽  
Treadmill Training ◽  
Vascular Regeneration ◽  
Apoptosis Protein ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Water Treadmill

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.

scholarly journals Water Treadmill Training Ameliorates Neurite Outgrowth Inhibition Associated With NGR/RhoA/ROCK by Inhibiting Astrocyte Activation Following Spinal Cord Injury

2021 ◽  
Author(s):  
Xinwang Ying ◽  
Xiaolan Yu ◽  
Jintao Zhu ◽  
Xuqing Li ◽  
Yujun Zheng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurite Outgrowth ◽  
Treadmill Training ◽  
Axonal Outgrowth ◽  
Astrocyte Activation ◽  
Nissl Staining ◽  
Quantitative Expression ◽  
Cord Injury ◽  
Water Treadmill

Abstract Background: Axons become scattered and incomplete after spinal cord injury (SCI). Cross-talk between astrocytes and neurons plays a pivotal role in neurite outgrowth following SCI. Rehabilitative training is a recognized method for the treatment of SCI, but the specific mechanism of its effect on axonal outgrowth in the central nervous system (CNS) has not been determined.Methods: A total of 160 adult male SD rats weighing 200–250 g were randomly divided into three groups, and an SCI animal model was established. Rats were subjected to water treadmill training (TT) for 7 or 14 d. The Basso-Beattie-Bresnahan (BBB) motor function scale, hematoxylin-eosin (HE) staining, Nissl staining, Western blotting and immunofluorescence were used to measure the degree of neurological deficit, tissue morphology, quantitative expression and accurate localization of the corresponding proteins.Results: We found that TT decreased tissue structure damage and improved functional recovery. TT promoted the regeneration of neurons and reduced apoptosis induced by SCI around the lesion. TT significantly increased the expression of GAP43 and NF200 after SCI. In addition, the injury-induced increase in the expression of proinflammatory factors was significantly inhibited by TT. TT reduced the activation of astrocytes and microglia, accompanied by reduced expression of C3d and higher increased of S100A10. Finally, the level of chondroitin sulfate proteoglycan (CSPG) surrounding the lesion and activation of the NGR/RhoA/ROCK signalling pathway in neurons after SCI were effectively inhibited by TT.Conclusions: In this study, we found that TT played a novel role in recovery from SCI by promoting axonal outgrowth associated with the NGR/RhoA/ROCK by inhibiting astrocyte activation after SCI.

scholarly journals Underwater-treadmill training attenuates blood-spinal cord barrier disruption by promoting angiogenesis and inhibiting MMP-2/9 expression following spinal cord injury

2020 ◽  
Author(s):  
Xinwang Ying ◽  
Qingfeng Xie ◽  
Shengcun Li ◽  
Xiaolan Yu ◽  
Kecheng Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Rating Scale ◽  
Vascular Endothelial Cells ◽  
Treadmill Training ◽  
Structure Damage ◽  
Vascular Regeneration ◽  
Transmission Electron ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier

Abstract Background The blood-spinal cord barrier (BSCB) can be seriously damaged after SCI and is considered to be a therapeutic target. 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 underwater-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 SCI models were established and randomly divided into three groups. Rats underwent TT after SCI. The degree of neurological deficit, water content, BSCB permeability, protein expression and ultrastructure of vascular endothelial cells were assessed by the BBB motor rating scale, haematoxylin-eosin (HE) staining, Evans blue (EB) 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 and improved functional recovery after SCI; TT prevent the loss of TJ and AJ protein; TT promotes angiogenesis and inhibits the expression of MMP-2 and MMP-9 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.

scholarly journals Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Focused Ultrasound ◽  
Healthy Tissue ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Intense Staining ◽  
Her2 Breast Cancer ◽  
Sprague Dawley Rats ◽  
Blood Spinal Cord Barrier

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

scholarly journals Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christian Blume ◽  
M. F. Geiger ◽  
M. Müller ◽  
H. Clusmann ◽  
V. Mainz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurological Status ◽  
Consecutive Series ◽  
Inflammatory Reactions ◽  
Immune Mediated ◽  
Elisa Testing ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Angiopoietin 2

AbstractEndogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

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