Source:http://linkedlifedata.com/resource/pubmed/id/19531375
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-8-17
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| pubmed:abstractText |
Cerebral ischemia/reperfusion injury is characterized by the development of inflammatory response, in which vascular macrophages and endogenous microglia are involved. Recent studies showed marked induction of hematopoietic prostaglandin D synthase (HPGDS) after ischemic/reperfusion injury and its localization in microglia, but the molecular mechanism(s) of HPGDS actions in cerebral ischemia is not clear. To clarify the role of HPGDS in cerebral ischemia, C57BL/6 mice and bone marrow chimera mice with cerebral ischemia/reperfusion injury were treated with (4-benzhydryloxy-(1) {3-(1H-tetrazol-5-yl)-propyl}piperidine (HQL-79), a specific inhibitor of HPGDS. The bone marrow chimera mice exhibit expression of enhanced green fluorescent protein (EGFP) in bone marrow/blood-derived monocytes/macrophages. Mice were subjected to ischemia/reperfusion and either treated with HQL-79 (n=44) or vehicle (n=44). Brain sections prepared at 72 h and 7 days after reperfusion were analyzed for neuronal nuclei (NeuN), HPGDS, ionized calcium-binding adapter molecule 1 (Iba1), inducible NO synthase (iNOS), nitrotyrosine, nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX-2). The mortality rate (80%) and infarct size were larger in HQL-79- than vehicle-treated mice (58.7+/-8.5 versus 45.2+/-4.9 mm(3); mean+/-SEM, P<0.0001) at 7 days after reperfusion. HQL-79 reduced NeuN expression in the transition area and Iba1 expression (P<0.0001) in the ischemic peri- and penumbra area, but increased COX-2 (P<0.05) and NF-kB expression (P<0.05) in ischemic penumbra and increased formation of nitrotyrosine (P<0.0001) and iNOS (P<0.0001) in the ischemic core area at 72 h and 7 days after reperfusion. In EGFP chimera mice, HQL-79 increased the migration of Iba1/EGFP-positive bone marrow-derived monocytes/macrophages, and simultaneously upregulated iNOS expression in the ischemic core area (P<0.0001), but increased intrinsic microglia/macrophages in ischemic peri-area and penumbra (P<0.0001) at 72 h and 7 days after reperfusion, suggesting involvement of monocytes/macrophages in HQL-79-induced expansion of ischemic injury. Our results demonstrated that the neuroprotective effects of HPGDS in our model are mediated by suppression of activation and infiltration of inflammatory cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-benzhydryloxy-1-(3-(1H-tetrazol-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intramolecular Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Isomerases,
http://linkedlifedata.com/resource/pubmed/chemical/Lipocalins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/prostaglandin R2 D-isomerase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1873-7544
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
29
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| pubmed:volume |
163
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
296-307
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| pubmed:meshHeading |
pubmed-meshheading:19531375-Animals,
pubmed-meshheading:19531375-Anti-Inflammatory Agents,
pubmed-meshheading:19531375-Biological Markers,
pubmed-meshheading:19531375-Bone Marrow Transplantation,
pubmed-meshheading:19531375-Brain,
pubmed-meshheading:19531375-Chemotaxis, Leukocyte,
pubmed-meshheading:19531375-Disease Models, Animal,
pubmed-meshheading:19531375-Encephalitis,
pubmed-meshheading:19531375-Enzyme Inhibitors,
pubmed-meshheading:19531375-Green Fluorescent Proteins,
pubmed-meshheading:19531375-Hypoxia-Ischemia, Brain,
pubmed-meshheading:19531375-Intramolecular Oxidoreductases,
pubmed-meshheading:19531375-Ischemic Attack, Transient,
pubmed-meshheading:19531375-Isomerases,
pubmed-meshheading:19531375-Lipocalins,
pubmed-meshheading:19531375-Macrophages,
pubmed-meshheading:19531375-Male,
pubmed-meshheading:19531375-Mice,
pubmed-meshheading:19531375-Mice, Inbred C57BL,
pubmed-meshheading:19531375-Microglia,
pubmed-meshheading:19531375-Nerve Tissue Proteins,
pubmed-meshheading:19531375-Neuroprotective Agents,
pubmed-meshheading:19531375-Nitric Oxide Synthase Type II,
pubmed-meshheading:19531375-Piperidines,
pubmed-meshheading:19531375-Reperfusion Injury,
pubmed-meshheading:19531375-Transplantation Chimera
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| pubmed:year |
2009
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| pubmed:articleTitle |
Protective role of hematopoietic prostaglandin D synthase in transient focal cerebral ischemia in mice.
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| pubmed:affiliation |
Research Institute for Disease of Old Age, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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