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Cited by 75Spinal Cord Injury ResearchBarrier Structure and Function StudiesProtease and Inhibitor Mechanisms

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Matrix Metalloproteinase-8 Inhibition Prevents Disruption of Blood–Spinal Cord Barrier and Attenuates Inflammation in Rat Model of Spinal Cord Injury

Kumar, Hemant, Jo, Min-Jae, Choi, Hyemin, Muttigi, Manjunatha S., Shon, Seil, Kim, Byung-Joo, Lee, Soo-Hong, Han, In-Bo·2018·Molecular Neurobiology
DOI 10.1007/s12035-017-0509-3
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Abstract

After spinal cord injury (SCI), tight junction (TJ) protein degradation increases permeability and disrupts the blood-spinal cord barrier (BSCB). The BSCB is primarily formed of endothelial cell, which forms a specialized tight seal due to the presence of TJs. BSCB disruption after SCI allows neutrophil infiltration. Matrix metalloproteinase (MMP)-8 is believed to be mainly expressed by neutrophils and is quickly released upon neutrophil activation. Here, we determined whether MMP-8 is involved in the TJ protein degradation in endothelial cells and also determined its role in the neuroinflammation after SCI. MMP-8 recombinant protein treatment increases the TNF-α expression and decreased the TJ (occludin and zonula occludens-1) protein expression in the endothelial cells. Likewise, specific MMP-8 inhibitor (MMP-8I) significantly prevented the TNF-α-induced decrease in the expression of TJ protein in endothelial cells. Furthermore, MMP-8 expression was significantly increased 1 and 3 days after moderate compression (35 g for 5 min at T10 level) SCI, whereas TJ protein levels decreased as determined qRT-PCR, western blotting, and immunohistochemistry. MMP-8 was inhibited directly using a MMP-8I (5 mg/kg) and indirectly by reducing neutrophil infiltration with sivelestat sodium (50 mg/kg) or using the antioxidant N-acetyl-L-cysteine (100 mg/kg). The MMP-8I significantly decreased TNF-α expression, IL-6, and iNOS expression and increased TJ protein expression after SCI. In additi…

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  • Blood-spinal cord barrier disruption following spinal cord injury allows white blood cells to infiltrate the injured parenchyma and contribute to secondary injury.

    “BSCB disruption following spinal cord injury (SCI) allows white blood cells to infiltrate the injured parenchyma and contribute to secondary injury (3, 239, 334, 692).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [334]

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Metadata

Authors
Kumar, H., Jo, M.-J., Choi, H., Muttigi, M. S., Shon, S., Kim, B.-J., Lee, S.-H., & Han, I.-B.
Affiliations
  • CHA University Bundang Medical Center (KR)
  • CHA University (KR)
Corresponding author
Lee, Soo-Hong
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2017-04-18
Volume
55
Issue
3
Pages
2577-2590
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-017-0509-3
OpenAlex
W2606215117
Cited by
75
References
6
Citations by year
2026: 4 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 15 · 2021: 14 · 2020: 9 · 2019: 4 · 2018: 5 · 2017: 2
FWCI
4.29
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation of Korea (NRF-2014R1A1A2059118, NRF2015H1D3A1066543)
  • Ministry of Science, ICT & Future Planning (NRF2016R1A2A1A05004987)
  • Healthcare Technology Research and Development (HI14C3270, HR16C0002)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
matrix metalloproteinase-8, spinal cord injury, blood-spinal cord barrier, endothelial cells, neuroinflammation, neutrophil infiltration, TNF-α, occludin, zonula occludens-1, sivelestat, N-acetylcysteine, Evans blue extravasation, inducible nitric oxide synthase, interleukin-6
MeSH terms
Animals, Blood-Brain Barrier, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Inflammation, Spinal Cord, Spinal Cord Injuries, Rats, Sprague-Dawley, Tight Junctions, Matrix Metalloproteinase 8, Rats, Matrix Metalloproteinase Inhibitors

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