Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice

Yoshinobu Wakisaka, Yi Chu, Jordan D. Miller, Gary A. Rosenberg, Donald D. Heistad

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)56-69
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1 2010
Externally publishedYes

Fingerprint

Cerebral Hemorrhage
Hypertension
Oxidative Stress
Angiotensin II
Matrix Metalloproteinases
Matrix Metalloproteinase 9
Inbred C57BL Mouse
Nitric Oxide Synthase
Brain Injuries
Norepinephrine
Theoretical Models
Stroke
Injections
Incidence

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. / Wakisaka, Yoshinobu; Chu, Yi; Miller, Jordan D.; Rosenberg, Gary A.; Heistad, Donald D.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 30, No. 1, 01.01.2010, p. 56-69.

Research output: Contribution to journalArticle

Wakisaka, Yoshinobu ; Chu, Yi ; Miller, Jordan D. ; Rosenberg, Gary A. ; Heistad, Donald D. / Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. In: Journal of Cerebral Blood Flow and Metabolism. 2010 ; Vol. 30, No. 1. pp. 56-69.
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