|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
2006-3-24
|
|
pubmed:abstractText |
Kallikrein cleaves low molecular weight kininogen to generate vasoactive kinins, which bind to the kinin B2 receptor, triggering a host of biological effects. Kallikrein gene delivery has been shown previously to reduce ischemia/reperfusion-induced cerebral infarction. In this study, we tested the hypothesis that the kinin B2 receptor plays a protective role in ischemic brain injury using kinin B2 receptor gene knockout (B2R-KO) mice subjected to middle cerebral artery occlusion (MCAO). The mortality rate and neurological deficit scores of B2R-KO mice (n=48) after MCAO were significantly increased compared with wild-type (WT) mice (n=40) when examined over a 14-day period. In addition, the infarct volume in B2R-KO mice was significantly larger than in WT mice at days 1 and 3 after MCAO. Similarly, apoptotic cells, detected by TUNEL labeling counterstained with propidium iodide, and caspase-3 activity in the ischemic brain increased significantly in B2R-KO mice at days 1 and 3 after MCAO. Furthermore, the accumulation of neutrophils in the ischemic brain of B2R-KO mice after MCAO increased when compared with WT mice and was associated with elevated tumor necrosis factor alpha expression. These alterations in B2R-KO mice correlated with decreased NO levels, Akt, and glycogen synthase kinase-3beta phosphorylation and increased nicotinamide-adenine dinucleotide oxidase activity. These results indicate that the kinin B2 receptor promotes survival and protects against brain injury by suppression of apoptosis and inflammation induced by ischemic stroke.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NADH, NADPH Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/NADH oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Bradykinin B2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
1524-4563
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
47
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
752-61
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:16534002-Animals,
pubmed-meshheading:16534002-Apoptosis,
pubmed-meshheading:16534002-Brain,
pubmed-meshheading:16534002-Brain Ischemia,
pubmed-meshheading:16534002-Cerebral Infarction,
pubmed-meshheading:16534002-Female,
pubmed-meshheading:16534002-Glycogen Synthase Kinase 3,
pubmed-meshheading:16534002-Male,
pubmed-meshheading:16534002-Mice,
pubmed-meshheading:16534002-Mice, Inbred C57BL,
pubmed-meshheading:16534002-Mice, Knockout,
pubmed-meshheading:16534002-Multienzyme Complexes,
pubmed-meshheading:16534002-NADH, NADPH Oxidoreductases,
pubmed-meshheading:16534002-Nervous System Diseases,
pubmed-meshheading:16534002-Neuroprotective Agents,
pubmed-meshheading:16534002-Neutrophil Infiltration,
pubmed-meshheading:16534002-Nitrates,
pubmed-meshheading:16534002-Nitrites,
pubmed-meshheading:16534002-Phosphorylation,
pubmed-meshheading:16534002-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16534002-Receptor, Bradykinin B2,
pubmed-meshheading:16534002-Stroke,
pubmed-meshheading:16534002-Tumor Necrosis Factor-alpha
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
Postischemic brain injury is exacerbated in mice lacking the kinin B2 receptor.
|
|
pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|
