Matrix Metalloproteinase-8 Inhibition Prevents Disruption of Blood-Spinal Cord Barrier and Attenuates Inflammation in Rat Model of Spinal Cord Injury
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kumar, Hemant | - |
dc.contributor.author | Jo, Min-Jae | - |
dc.contributor.author | Choi, Hyemin | - |
dc.contributor.author | Muttigi, Manjunatha S. | - |
dc.contributor.author | Shon, Seil | - |
dc.contributor.author | Kim, Byung-Joo | - |
dc.contributor.author | Lee, Soo-Hong | - |
dc.contributor.author | Han, In-Bo | - |
dc.date.accessioned | 2021-06-18T07:43:12Z | - |
dc.date.available | 2021-06-18T07:43:12Z | - |
dc.date.issued | 2018-03 | - |
dc.identifier.issn | 0893-7648 | - |
dc.identifier.issn | 1559-1182 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45312 | - |
dc.description.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-alpha 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-alpha-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-alpha expression, IL-6, and iNOS expression and increased TJ protein expression after SCI. In addition, MMP-8I significantly lessens the amount of Evans blue dye extravasation observed after injury. Thus, our result suggests that MMP-8 plays an imperative role in inflammation and degradation of TJ proteins. Increased MMP-8 expression was associated with the early inflammatory phase of SCI. Inhibiting MMP-8 significantly attenuated SCI-induced inflammation, BSCB breakdown, and cell injury. | - |
dc.format.extent | 14 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | HUMANA PRESS INC | - |
dc.title | Matrix Metalloproteinase-8 Inhibition Prevents Disruption of Blood-Spinal Cord Barrier and Attenuates Inflammation in Rat Model of Spinal Cord Injury | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s12035-017-0509-3 | - |
dc.identifier.bibliographicCitation | MOLECULAR NEUROBIOLOGY, v.55, no.3, pp 2577 - 2590 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000426897800061 | - |
dc.identifier.scopusid | 2-s2.0-85017592094 | - |
dc.citation.endPage | 2590 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 2577 | - |
dc.citation.title | MOLECULAR NEUROBIOLOGY | - |
dc.citation.volume | 55 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | MMP-8 | - |
dc.subject.keywordAuthor | Spinal cord injury | - |
dc.subject.keywordAuthor | Tight junctions | - |
dc.subject.keywordAuthor | Occludin | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordAuthor | Blood-spinal cord barrier | - |
dc.subject.keywordPlus | EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS | - |
dc.subject.keywordPlus | BRAIN-BARRIER | - |
dc.subject.keywordPlus | FUNCTIONAL RECOVERY | - |
dc.subject.keywordPlus | HEME OXYGENASE-1 | - |
dc.subject.keywordPlus | NEUTROPHIL INFILTRATION | - |
dc.subject.keywordPlus | CEREBRAL-ISCHEMIA | - |
dc.subject.keywordPlus | VASCULAR EVENTS | - |
dc.subject.keywordPlus | CELL JUNCTIONS | - |
dc.subject.keywordPlus | MESSENGER-RNA | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.