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Article
Ischemia-Induced Brain Damage is Enhanced in Human Renin and Angiotensinogen Double-Transgenic Mice
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology
  • Shuzhen Chen, Wright State University - Main Campus
  • Guangze Li, Wright State University - Main Campus
  • Wenfeng Zhang, Wright State University - Main Campus
  • Jinju Wang
  • Curt D. Sigmund
  • James E. Olson, Wright State University - Main Campus
  • Yanfang Chen, Wright State University - Main Campus
Document Type
Article
Publication Date
11-1-2009
Abstract
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 μmol/l) abolished OGD-induced exaggeration of cell injury seen in R+A+ mice. The data indicate that activation of ANG II/AT1 signaling is harmful to brain exposed to ischemia.
DOI
10.​1152/​ajpregu.​91040.​2008
Citation Information
Shuzhen Chen, Guangze Li, Wenfeng Zhang, Jinju Wang, et al.. "Ischemia-Induced Brain Damage is Enhanced in Human Renin and Angiotensinogen Double-Transgenic Mice" American Journal of Physiology - Regulatory, Integrative and Comparative Physiology Vol. 297 Iss. 5 (2009) p. R1526 - R1531 ISSN: 0363-6119
Available at: http://works.bepress.com/james_olson/34/