The correlation between hypoxia-inducible factor-1α, matrix metalloproteinase-9 and functional recovery following chronic spinal cord compression

2019 ◽  
Vol 1718 ◽  
pp. 75-82 ◽  
Author(s):  
Xing Cheng ◽  
Houqing Long ◽  
Wenli Chen ◽  
Jinghui Xu ◽  
Xiaobo Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Matrix Metalloproteinase ◽  
Spinal Cord Compression ◽  
Functional Recovery ◽  
Hypoxia Inducible Factor ◽  
Cord Compression ◽  
Matrix Metalloproteinase 9 ◽  
Hypoxia Inducible Factor 1Α ◽  
Metalloproteinase 9

scholarly journals Assessment of Nogo-66 Receptor 1 Function In Vivo After Spinal Cord Injury

Neurosurgery ◽  
2014 ◽  
Vol 75 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jing Tong ◽  
Yi Ren ◽  
Xiaowei Wang ◽  
Vassilios G. Dimopoulos ◽  
Henry N. Kesler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Matrix Metalloproteinase ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Matrix Metalloproteinase 9 ◽  
Mutant Mice ◽  
Locomotor Function ◽  
Cord Injury ◽  
Metalloproteinase 9

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.

scholarly journals Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1α through Inducing High Expression of Matrix Metalloproteinase-9

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Huili Li ◽  
He Huang ◽  
Yunliang Cui ◽  
Weiwei Li ◽  
Shuliu Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Promoter Region ◽  
Hypoxia Inducible Factor ◽  
High Expression ◽  
Capillary Leakage ◽  
Sirna Transfection ◽  
Hypoxia Response ◽  
Hypoxia Inducible Factor 1Α ◽  
Metalloproteinase 9

Purposes. This study mainly explored the mechanism of capillary leakage caused by hypoxia-inducible factor-1α through inducing high expression of matrix metalloproteinase-9. Method. We established a monolayer endothelial cell model by culturing human umbilical vein endothelial cells (HUVEC) in vitro, used tumor necrosis factor (TNFα) and HIF-1α inhibitor 2-methoxyestradiol (2ME2) to act on HUVEC, and at the same time constructed siRNA-transfected HUVEC to interfere with the expression of HIF-1α. The permeability of monolayer endothelial cells was measured by transwell chamber method, the concentration of MMP-9 in the supernatant was measured by ELISA method, the expression of key molecules related to permeability (HIF- 1α, MMP-9, claudin-5, and ZO-1) was measured by RT-PCR and Western blot method, and the localization and expression of claudin-5 and ZO-1 were measured by immunofluorescence method. We searched for 7 HIF-1α hypoxia response elements within 4000 bp before the transcription start site in the MMP-9 promoter region, constructed the MMP-9 promoter-luciferase reporter gene recombinant plasmid, transfected and stimulated HUVEC with TNFα, and detected the effect of 7 hypoxia response element plasmids on the transcription activity of MMP-9 promoter. Results. Under the action of TNFα, the permeability of monolayer endothelial cells increased, and the concentration of MMP-9 in the cell supernatant increased. 2ME2 and HIF-1α-siRNA transfection can improve the above situation ( P < 0.05 ). 2ME2 and HIF-1α-siRNA transfection can inhibit the high expression of HIF-1α and MMP-9 caused by TNFα, thereby increasing the expression of claudin-5 and ZO-1 ( P < 0.05 ). 2ME2 and HIF-1α-siRNA transfection can reduce the inhibition of TNFα on the expression of cell membrane protein claudin-5 and tight junction protein ZO-1. Element 1, element 5, and element 7 are the sites where HIF-1α interacts with MMP-9 at the transcription level. Conclusion. This study shows that HIF-1α can increase the permeability of monolayer epithelial cells by inducing the high expression of MMP-9, leading to capillary leakage. Its target is at the −3798 bp, −1878 bp, and −1489 bp points of the transcription initiation site in the MMP-9 promoter region.

The value of decompression for acute experimental spinal cord compression injury

1980 ◽  
Vol 53 (6) ◽  
pp. 749-755 ◽  
Author(s):  
Eugen J. Dolan ◽  
Charles H. Tator ◽  
Laszlo Endrenyi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Functional Recovery ◽  
Cord Compression ◽  
Compression Method ◽  
Compression Injury ◽  
Inclined Plane ◽  
Content Type ◽  
Plane Technique ◽  
The Relationship

✓ A clip compression method was used to produce acute spinal cord compression injury in rats. The force and duration of the spinal cord compression were independently varied, and functional recovery of the cord was assessed using the inclined plane technique. Mathematical modeling produced a curve defining the relationship between force, duration, and functional recovery for each week after injury. The study clearly showed the beneficial effect of decompression and that increasing either the force or duration of compression, or both, caused a reduction in recovery.

scholarly journals Matrix Metalloproteinase-9 Facilitates Glial Scar Formation in the Injured Spinal Cord

2008 ◽  
Vol 28 (50) ◽  
pp. 13467-13477 ◽  
Author(s):  
J.-Y. C. Hsu ◽  
L. Y. W. Bourguignon ◽  
C. M. Adams ◽  
K. Peyrollier ◽  
H. Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Matrix Metalloproteinase ◽  
Glial Scar ◽  
Matrix Metalloproteinase 9 ◽  
Scar Formation ◽  
Injured Spinal Cord ◽  
Metalloproteinase 9
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