Neonatal stroke in mice causes long-term changes in neuronal Notch-2 expression that may contribute to prolonged injury.
Stroke
; 41(10 Suppl): S64-71, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20876509
ABSTRACT
BACKGROUND AND PURPOSE:
Notch receptors (1-4) are membrane proteins that, on ligand stilumation, release their cytoplasmic domains to serve as transcription factors. Notch-2 promotes proliferation both during development and cancer, but its role in response to ischemic injury is less well understood. The purpose of this study was to understand whether Notch-2 is induced after neonatal stroke and to investigate its functional relevance.METHODS:
P12 CD1 mice were subjected to permanent unilateral (right-sided) double ligation of the common carotid artery.RESULTS:
Neonatal ischemia induces a progressive brain injury with prolonged apoptosis and Notch-2 up-regulation. Notch-2 expression was induced shortly after injury in hippocampal areas with elevated c-fos activation and increased cell death. Long-term induction of Notch-2 also occurred in CA1 and CA3 in and around areas of cell death, and had a distinct pattern of expression as compared to Notch-1. In vitro oxygen glucose deprivation treatment showed a similar increase in Notch-2 in apoptotic cells. In vitro gain of function experiments, using an active form of Notch-2, show that Notch-2 induction is neurotoxic to a comparable extent as oxygen glucose deprivation treatment.CONCLUSIONS:
These results suggest that Notch-2 up-regulation after neonatal ischemia is detrimental to neuronal survival.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
/
Acidente Vascular Cerebral
/
Receptor Notch2
/
Hipocampo
/
Neurônios
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Stroke
Ano de publicação:
2010
Tipo de documento:
Article