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Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption?
DC Field | Value | Language |
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dc.contributor.author | 김경환 | - |
dc.date.accessioned | 2015-07-15T16:39:26Z | - |
dc.date.available | 2015-07-15T16:39:26Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/113335 | - |
dc.description.abstract | Blood-brain barrier (BBB) dysfunction is a potential mechanism involved in progressive striatal damage induced by the mitochondrial excitotoxin, 3-nitropropionic acid (3-NP). After activation by proteases and free radicals, matrix metalloproteinases (MMPs), particularly MMP-9 and -2, can digest the endothelial basal lamina leading to BBB opening. Using CD-1 mice, we show that MMP-9 expression by zymography is increased in the injured striatum compared with the contralateral striatum 2 hr after 3-NP injection [133.50 ± 57.17 vs 50.25 ± 13.56; mean ± SD of optical densities in arbitrary units (A.U.); p < 0.005] and remains elevated until 24 hr (179.33 ± 78.24 A.U.). After 4 hr, MMP-9 expression and activation are accompanied by an increase in BBB permeability. MMP inhibition attenuates BBB disruption, swelling, and lesion volume compared with vehicle-treated controls. There is a clear spatial relationship between MMP-9 expression and oxidized hydroethidine, indicating reactive oxygen species (ROS) production. Furthermore, transgenic mice that overexpress copper/zinc-superoxide dismutase (SOD1) show decreased lesion size and edema along with decreased immunoreactivity for MMP-9, compared with wild-type littermates (lesion: 38.8 ± 15.1 and 53.3 ± 10.3, respectively, p ≤ 0.05; edema: 21.8 ± 11.2 and 35.28 ± 11, respectively, p ≤ 0.05; MMP-9-positive cells: 352 ± 57 and 510 ± 45, respectively, p ≤ 0.005), whereas knock-out mice deficient in SOD1 display significantly greater swelling (48.65 ± 17; p ≤ 0.05). We conclude that early expression and activation of MMP-9 by ROS may be involved in early BBB disruption and progressive striatal damage after 3-NP treatment. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.relation.isPartOf | JOURNAL OF NEUROSCIENCE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | matrix metalloproteinase | - |
dc.subject.MESH | 3-nitropropionic acid | - |
dc.subject.MESH | blood– brain barrier | - |
dc.subject.MESH | Evans blue extravasation | - |
dc.subject.MESH | oxidative stress | - |
dc.subject.MESH | striatum | - |
dc.title | Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption? | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurology (신경과학) | - |
dc.contributor.googleauthor | Gyung W. Kim | - |
dc.contributor.googleauthor | Yvan Gasche | - |
dc.contributor.googleauthor | Pak H. Chan | - |
dc.contributor.googleauthor | Carolina M. Maier | - |
dc.contributor.googleauthor | Jean-Christophe Copin | - |
dc.contributor.googleauthor | Susanna Grzeschik | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00310 | - |
dc.relation.journalcode | J01633 | - |
dc.identifier.eissn | 1529-2401 | - |
dc.subject.keyword | matrix metalloproteinase | - |
dc.subject.keyword | 3-nitropropionic acid | - |
dc.subject.keyword | blood– brain barrier | - |
dc.subject.keyword | Evans blue extravasation | - |
dc.subject.keyword | oxidative stress | - |
dc.subject.keyword | striatum | - |
dc.contributor.alternativeName | Kim, Gyung Whan | - |
dc.contributor.affiliatedAuthor | Kim, Gyung Whan | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 23 | - |
dc.citation.number | 25 | - |
dc.citation.startPage | 8733 | - |
dc.citation.endPage | 8742 | - |
dc.identifier.bibliographicCitation | JOURNAL OF NEUROSCIENCE, Vol.23(25) : 8733-8742, 2003 | - |
dc.identifier.rimsid | 55840 | - |
dc.type.rims | ART | - |
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