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.
Original language | English (US) |
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Pages (from-to) | S64-S71 |
Journal | Stroke |
Volume | 41 |
Issue number | 10 SUPPL. 1 |
DOIs | |
State | Published - Oct 2010 |
Keywords
- Notch-2
- apoptosis
- c-fos
- hippocampus
- neonatal stroke
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
- Advanced and Specialized Nursing