Journal article
Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice
Journal of cerebral blood flow and metabolism, Vol.30(1), pp.56-69
01/2010
DOI: 10.1038/jcbfm.2009.183
PMCID: PMC2888049
PMID: 19724290
Abstract
Oxidative stress and matrix metalloproteinases (MMPs) contribute to hemorrhagic transformation after ischemic stroke and brain injury after intracerebral hemorrhage (ICH). The goal of this study was to develop a new model of spontaneous ICH, based on the hypothesis that acute, superimposed on chronic, hypertension produces ICH. We hypothesized that increases in angiotensin II (AngII)-mediated oxidative stress and activation of MMPs are associated with, and may precede, spontaneous ICH during hypertension. In C57BL/6 mice, chronic hypertension was produced with AngII infusion and an inhibitor of nitric oxide synthase. During chronic hypertension, mice with acute hypertension from injections of AngII developed ICH. Oxidative stress and MMP levels increased in the brain even before developing ICH. Active MMPs colocalized with a marker of oxidative stress, especially on cerebral vessels that appeared to lead toward regions with ICH. Incidence of ICH and levels of oxidative stress and MMP-9 were greater in mice with acute hypertension produced by AngII than by norepinephrine. In summary, we have developed an experimental model of ICH during hypertension that may facilitate studies in genetically altered mice. We speculate that acute hypertension, especially when induced by AngII, may be critical in spontaneous ICH during chronic hypertension, possibly through oxidative stress and MMP-9.
Details
- Title: Subtitle
- Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice
- Creators
- Yoshinobu Wakisaka - , Iowa City, IowaYi Chu - , Iowa City, IowaJordan D Miller - , Iowa City, IowaGary A Rosenberg - , Albuquerque, New MexicoDonald D Heistad - , Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of cerebral blood flow and metabolism, Vol.30(1), pp.56-69
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/jcbfm.2009.183
- PMID
- 19724290
- PMCID
- PMC2888049
- ISSN
- 0271-678X
- eISSN
- 1559-7016
- Alternative title
- Oxidative stress, MMP-9, and brain hemorrhage
- Language
- English
- Date published
- 01/2010
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040359802771
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