Neonatal stroke in mice causes long-term changes in neuronal Notch-2 expression that may contribute to prolonged injury.

Mark McIntosh,'s picture
PubMed URL: 
http://www.ncbi.nlm.nih.gov/pubmed/20876509
Author: 
Comi AM
Author List: 
Albéri L
Chi Z
Kadam SD
Mulholland JD
Dawson VL
Gaiano N
Comi AM
Journal: 
Stroke
PubMed ID: 
20876509
Pagination: 
S64-71
Volume: 
41
Issue: 
10 Suppl
Abstract: 
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.P12 CD1 mice were subjected to permanent unilateral (right-sided) double ligation of the common carotid artery.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.These results suggest that Notch-2 up-regulation after neonatal ischemia is detrimental to neuronal survival.
Published Date: 
October, 2010

Bradley L. Schlaggar, M.D., Ph.D., Named President and CEO of Kennedy Krieger Institute

We’re thrilled to welcome Bradley L. Schlaggar, M.D., Ph.D., to the Kennedy Krieger family as our next President and CEO.

Learn more.

Appointments & Referrals

FIND A SPECIALIST

Publications

Read inspiring stories, news and updates about the Institute's patient care, research, special education, professional training, and community programs.

 

Resource Finder

 

A free resource that provides access to information and support for individuals and families living with developmental disabilities.