Linked Life Data

14507973

Source:http://linkedlifedata.com/resource/pubmed/id/14507973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2003-9-25
pubmed:abstractText
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 < or = 0.05; edema: 21.8 +/- 11.2 and 35.28 +/- 11, respectively, p < or = 0.05; MMP-9-positive cells: 352 +/- 57 and 510 +/- 45, respectively, p < or = 0.005), whereas knock-out mice deficient in SOD1 display significantly greater swelling (48.65 +/- 17; p < or = 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8733-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14507973-Animals, pubmed-meshheading:14507973-Behavior, Animal, pubmed-meshheading:14507973-Blood-Brain Barrier, pubmed-meshheading:14507973-Brain Edema, pubmed-meshheading:14507973-Corpus Striatum, pubmed-meshheading:14507973-Guanosine, pubmed-meshheading:14507973-Immunohistochemistry, pubmed-meshheading:14507973-Male, pubmed-meshheading:14507973-Matrix Metalloproteinase 2, pubmed-meshheading:14507973-Matrix Metalloproteinase 9, pubmed-meshheading:14507973-Mice, pubmed-meshheading:14507973-Mice, Knockout, pubmed-meshheading:14507973-Mitochondria, pubmed-meshheading:14507973-Motor Activity, pubmed-meshheading:14507973-Neurodegenerative Diseases, pubmed-meshheading:14507973-Nitro Compounds, pubmed-meshheading:14507973-Oxidative Stress, pubmed-meshheading:14507973-Propionic Acids, pubmed-meshheading:14507973-Superoxide Dismutase
pubmed:year
2003
pubmed:articleTitle
Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption?
pubmed:affiliation
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California 94305-5487, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't