Source:http://linkedlifedata.com/resource/pubmed/id/20047900
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
Pt 2
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| pubmed:dateCreated |
2010-2-17
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| pubmed:abstractText |
Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system associated with autoantibodies against the glial water channel protein aquaporin-4. It has recently been reported that immunoglobulin from neuromyelitis optica patients injected peripherally does not cause lesions in naive rats, but only when pre-existing central nervous system inflammation is present. Here, we investigated whether immunoglobulin G from aquaporin-4-autoantibody-positive neuromyelitis optica patients has the potential to damage the central nervous system either alone or in the presence of human complement. Immunoglobulin G from neuromyelitis optica patients did not activate mouse complement and was not pathogenic when injected into mouse brain. However, co-injection of immunoglobulin G from neuromyelitis optica patients with human complement produced neuromyelitis optica-like lesions in mice. Within 12 h of co-injecting immunoglobulin G from neuromyelitis optica patients and human complement, there was a striking loss of aquaporin-4 expression, glial cell oedema, myelin breakdown and axonal injury, but little intra-parenchymal inflammation. At 7 days, there was extensive inflammatory cell infiltration, perivascular deposition of activated complement components, extensive demyelination, loss of aquaporin-4 expression, loss of reactive astrocytes and neuronal cell death. In behavioural studies, mice injected with immunoglobulin G from neuromyelitis optica patients and human complement into the right hemisphere preferentially turned to the right at 7 days. No brain inflammation, demyelination or right-turning behaviour was seen in wild-type mice that received immunoglobulin G from non-neuromyelitis optica patients with human complement, or in aquaporin-4-null mice that received immunoglobulin G from neuromyelitis optica patients with human complement. We conclude that co-injection of immunoglobulin G from neuromyelitis optica patients with human complement reproduces the key histological features of neuromyelitis optica and that aquaporin-4 is necessary and sufficient for immunoglobulin G from neuromyelitis optica patients to exert its effect. In our mouse model, immunoglobulin G from neuromyelitis optica patients does not require pre-existing central nervous system inflammation to produce lesions.
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| pubmed:grant | |
| pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20047900-9276712
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1460-2156
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
133
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
349-61
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| pubmed:dateRevised |
2011-7-22
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| pubmed:meshHeading |
pubmed-meshheading:20047900-Animals,
pubmed-meshheading:20047900-Aquaporin 4,
pubmed-meshheading:20047900-Autoantibodies,
pubmed-meshheading:20047900-CHO Cells,
pubmed-meshheading:20047900-Complement System Proteins,
pubmed-meshheading:20047900-Cricetinae,
pubmed-meshheading:20047900-Cricetulus,
pubmed-meshheading:20047900-Disease Models, Animal,
pubmed-meshheading:20047900-Humans,
pubmed-meshheading:20047900-Immunoglobulin G,
pubmed-meshheading:20047900-Injections, Intraventricular,
pubmed-meshheading:20047900-Mice,
pubmed-meshheading:20047900-Mice, Knockout,
pubmed-meshheading:20047900-Neuromyelitis Optica
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| pubmed:year |
2010
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| pubmed:articleTitle |
Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice.
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| pubmed:affiliation |
St George's, University of London, London SW17 0RE, UK.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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