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  Endogenous TLR4 agonists Mrp-8 &-14 mediate CNS injury in focal cerebral ischemia.

Gina, G., Prinz, V., Albrecht, M. W., Harhausen, D., Khojasteh, U., Nacken, W., et al. (2009). Endogenous TLR4 agonists Mrp-8 &-14 mediate CNS injury in focal cerebral ischemia. Mitochondrial Disease, 1198-1204. doi:doi:10.1016/j.bbadis.2009.10.003.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7CEE-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7CEF-9
Genre: Journal Article
Alternative Title : BBA

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1792.pdf (Any fulltext), 608KB
 
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 Creators:
Gina, Gina1, Author
Prinz, Vincent, Author
Albrecht, Marcus W.1, Author
Harhausen, Denise, Author
Khojasteh, Uldus, Author
Nacken, Wolfgang, Author
Endrese, Matthias, Author
Dirnagl, Ulrich, Author
Nietfeld, Wilfried2, Author              
Trendelenburg, George, Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: S100A8; S100A9; Toll-like receptor; MCAO; Knockout mice
 Abstract: Several reports have recently demonstrated a detrimental role of Toll-like receptors (TLR) in cerebral ischemia, while there is little information about the endogenous ligands which activate TLR-signaling. The myeloid related proteins-8 and-14 (Mrp8/S100A8; Mrp14/S100A9) have recently been characterized as endogenous TLR4-agonists, and thus may mediate TLR-activation in cerebral ischemia. Interestingly, not only TLR-mRNAs, but also Mrp8 and Mrp14 mRNA were found to be induced in mouse brain between 3 and 48 h after transient 1 h focal cerebral ischemia/reperfusion. Mrp-protein was expressed in the ischemic hemisphere, and co-labeled with CD11b-positive cells. To test the hypothesis that Mrp-signaling contributes to the postischemic brain damage, we subjected Mrp14-deficient mice, which also lack Mrp8 protein expression, to focal cerebral ischemia. Mrp14-deficient mice had significantly smaller lesion volumes when compared to wild-type littermates (130 ± 16 mm3 vs. 105 ± 28 mm3) at 2 days after transient focal cerebral ischemia (1 h), less brain swelling, and a reduced macrophage/microglia cell count in the ischemic hemisphere. We conclude that upregulation and signaling of Mrp-8 and-14 contribute to neuroinflammation and the progression of ischemic damage.

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Language(s): eng - English
 Dates: 2009-10-14
 Publication Status: Published in print
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Title: Mitochondrial Disease
Source Genre: Issue
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Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 1198 - 1204 Identifier: -

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Title: Biochimica et Bioysica Acta (BBA) - Molecular Basis of Disease
  Alternative Title : BBA
Source Genre: Journal
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Pages: - Volume / Issue: 1792 (12) Sequence Number: - Start / End Page: - Identifier: ISSN: 0006-3002