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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-11-2
pubmed:abstractText
To investigate the role of brain angiotensin II (ANG II) in the pathogenesis of injury following ischemic stroke, mice overexpressing renin and angiotensinogen (R+A+) and their wild-type control animals (R-A-) were used for experimental ischemia studies. Focal brain ischemia was induced by middle cerebral artery occlusion (MCAO). The severity of ischemic injury was determined by measuring neurological deficits and histological damage at 24 and 48 h after MCAO, respectively. To exclude the influence of blood pressure and local collateral blood flow, brain slices were used for oxygen and glucose deprivation (OGD) studies. The severity of OGD-induced damage was determined by measuring indicators of tissue swelling and cell death, the intensity of the intrinsic optical signal (IOS), and the number of propidium iodide (PI) staining cells, respectively. Results showed 1) R+A+ mice showed higher neurological deficit score (3.8 +/- 0.5 and 2.5 +/- 0.3 for R+A+ and R-A-, respectively, P < 0.01) and larger infarct volume (22.2 +/- 1.6% and 14.1 +/- 1.2% for R+A+ and R-A-, respectively, P < 0.01); 2) The R+A+ brain slices showed more severe tissue swelling and cell death in the cortex (IOS: 140 +/- 6% and 114 +/- 10%; PI: 139 +/- 20 cells/field and 39 +/- 9 cells/field for R+A+ and R-A-, respectively, P < 0.01); 3) treatment with losartan (20 micromol/l) abolished OGD-induced exaggeration of cell injury seen in R+A+ mice. The data indicate that activation of ANG II/AT(1) signaling is harmful to brain exposed to ischemia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1522-1490
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1526-31
pubmed:dateRevised
2010-11-2
pubmed:meshHeading
pubmed-meshheading:19759335-Angiotensin II, pubmed-meshheading:19759335-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:19759335-Angiotensinogen, pubmed-meshheading:19759335-Animals, pubmed-meshheading:19759335-Blood Pressure, pubmed-meshheading:19759335-Brain, pubmed-meshheading:19759335-Brain Ischemia, pubmed-meshheading:19759335-Cell Death, pubmed-meshheading:19759335-Disease Models, Animal, pubmed-meshheading:19759335-Humans, pubmed-meshheading:19759335-Infarction, Middle Cerebral Artery, pubmed-meshheading:19759335-Losartan, pubmed-meshheading:19759335-Male, pubmed-meshheading:19759335-Mice, pubmed-meshheading:19759335-Mice, Transgenic, pubmed-meshheading:19759335-Receptor, Angiotensin, Type 1, pubmed-meshheading:19759335-Regional Blood Flow, pubmed-meshheading:19759335-Renin, pubmed-meshheading:19759335-Severity of Illness Index, pubmed-meshheading:19759335-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Ischemia-induced brain damage is enhanced in human renin and angiotensinogen double-transgenic mice.
pubmed:affiliation
Departments of Pharmacology and Toxicology, Wright State University, Dayton, Ohio, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural