Molecular mechanisms by which stroke increases neurogenesis have not been fully 
investigated. Using neural progenitor cells isolated from the subventricular 
zone (SVZ) of the adult rat subjected to focal cerebral ischemia, we 
investigated the Notch pathway in regulating proliferation and differentiation 
of adult neural progenitor cells after stroke. During proliferation of neural 
progenitor cells, ischemic neural progenitor cells exhibited substantially 
increased levels of Notch, Notch intracellular domain (NICD), and hairy enhancer 
of split (Hes) 1, which was associated with a significant increase of 
proliferating cells. Blockage of the Notch pathway by short interfering 
ribonucleic acid (siRNA) against Notch or a gamma secretase inhibitor 
significantly reduced Notch, NICD and Hes1 expression and cell proliferation 
induced by stroke. During differentiation of neural progenitor cells, Notch and 
Hes1 expression was downregulated in ischemic neural progenitor cells, which was 
coincident with a significant increase of neuronal population. Inhibition of the 
Notch pathway with a gamma secretase inhibitor further substantially increased 
neurons, but did not alter astrocyte population in ischemic neural progenitor 
cells. These data suggest that the Notch signaling pathway mediates adult SVZ 
neural progenitor cell proliferation and differentiation after stroke.