Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage.
Am J Pathol
; 178(4): 1749-61, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21435456
ABSTRACT
Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of morbidity and mortality. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in regulating signal transduction and cholesterol trafficking in cells. Although a recent study suggests a protective role of Cav-1 in cerebral ischemia, its function in ICH remains unknown. In this study, we examined the role of Cav-1 and in a model of collagenase-induced ICH and in neuronal cultures. Our results indicate that Cav-1 was up-regulated in the perihematomal area predominantly in endothelial cells. Cav-1 knockout mice had smaller injury volumes, milder neurologic deficits, less brain edema, and neuronal death 1 day after ICH than wild-type mice. The protective mechanism in Cav-1 knockout mice was associated with marked reduction in leukocyte infiltration, decreased expression of inflammatory mediators, including macrophage inflammatory protein (MIP)-2 and cyclooxygenase (COX)-2, and reduced matrix metalloproteinase-9 activity. Deletion of Cav-1 also suppressed heme oxygenase-1 expression and attenuated reactive oxygen species production after ICH. Moreover, deletion or knockdown of Cav-1 decreased neuronal vulnerability to hemin-induced toxicity and reduced heme oxygenase (HO)-1 induction in vitro. These data suggest that Cav-1 plays a deleterious role in early brain injury after ICH. Inhibition of Cav-1 may provide a novel therapeutic approach for the treatment of hemorrhagic stroke.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Hemorragia Cerebral
/
Deleção de Genes
/
Caveolina 1
Limite:
Animals
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Taiwan