Document Detail


Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice.
MedLine Citation:
PMID:  19724290     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yoshinobu Wakisaka; Yi Chu; Jordan D Miller; Gary A Rosenberg; Donald D Heistad
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-09-02
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  30     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-04     Completed Date:  2010-02-03     Revised Date:  2011-07-20    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  56-69     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Cardiovascular Center, University of Iowa, Iowa City, Iowa 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Angiotensin II
Animals
Blood Pressure / physiology
Chronic Disease
Fluorescent Antibody Technique
Gelatin
Hypertension / chemically induced,  complications*,  pathology
Immunohistochemistry
Intracranial Hemorrhages / etiology*,  pathology
Male
Matrix Metalloproteinases / metabolism
Mice
Mice, Inbred C57BL
Norepinephrine
Oxidative Stress / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Stroke / pathology
Vasoconstrictor Agents
Grant Support
ID/Acronym/Agency:
F32 HL086160-02/HL/NHLBI NIH HHS; HL62984/HL/NHLBI NIH HHS; K99 HL092235-01/HL/NHLBI NIH HHS; NS24621/NS/NINDS NIH HHS; R00 HL092235-02/HL/NHLBI NIH HHS; R00 HL092235-03/HL/NHLBI NIH HHS; R00 HL092235-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; 51-41-2/Norepinephrine; 9000-70-8/Gelatin; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

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