Pretreatment with
estrogen has been shown to increase subventricular zone (SVZ) neurogenesis and improve neurological outcome after
cerebral ischemia reperfusion injury in mice. However, the potential of post-
stroke estrogen administration to enhance neurogenesis is largely unknown. In this study, we explored whether post-
stroke estradiol administration had any effect on SVZ neurogenesis in a rat model of permanent focal
cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats (250-280 g) were divided into
sham-operated (n=10), control (n=40), and
estradiol-treated (n=40) groups. 5-Bromo-2-deoxyuridine (
BrdU) was used to label proliferating cells. Immunohistochemistry was used to detect neurogenesis in the ischemic ipsilateral SVZ at 1, 3, 7 and 14 days following
ischemia. The
protein levels of
hypoxia-inducible factor 1α (HIF-1α), and
vascular endothelial growth factor (
VEGF) in ischemic ipsilateral SVZ were determined by Western blotting at 6, 12, 24 and 72h after
ischemia. Improved behavioral deficits and reduced
infarct size were seen in
estradiol-treated rats (P<0.05). Post-
stroke estradiol administration increased
BrdU-labeled cells,
nestin-positive cells, doublecortin (DCX)-positive cells and
BrdU+/DCX+ cells in the ischemic ipsilateral SVZ at all time points (P<0.05). Treatment with
estradiol also increased HIF-1α and
VEGF protein levels in the ischemic ipsilateral SVZ at all time points examined (P<0.05). These findings indicate that post-
stroke estradiol administration promotes SVZ neurogenesis in rats, probably by increasing HIF-1α and
VEGF protein expression.