http://link.springer.com/article/10.1007/s12035-015-9651-y
Abstract
Studies have shown
that progesterone enhances functional recovery after ischemic stroke,
but the underlying mechanisms are not completely understood. Therefore,
we investigated the effect of progesterone on vascular endothelial
growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and
neurogenesis in a rodent stroke model. Rats underwent permanent middle
cerebral artery occlusion (pMCAO) and then received intraperitoneal
injections of progesterone (15 mg/kg) or vehicle at 1 h followed by
subcutaneous injections at 6, 24, and 48 h. We examined VEGF and BDNF
expression by Western blotting and/or immunostaining and microvessel
density by lectin immunostaining. Neurogenesis in the subventricular
zone was determined by immunostaining of Ki67 and doublecortin, and
double BrdU/Nestin immunostaining. We calculated brain water content
with the wet-dry weight method on day 3 and assessed neurologic deficits
with the modified neurological severity score on days 1, 3, 7, and 14.
Progesterone-treated rats showed a significant decrease in VEGF
expression, but an increase in BDNF expression, compared with that of
vehicle-treated pMCAO rats on day 3 post-occlusion. Progesterone did not
alter the microvessel density, but it reduced brain water content
compared with that in vehicle-treated rats on day 3 post-occlusion.
Progesterone treatment increased the numbers of newly generated neurons
in the subventricular zone and doublecortin-positive cells in the
peri-infarct region on day 7 post-occlusion. In addition, progesterone
improved neurologic function on days 7 and 14 post-occlusion. Our data
suggest that the enhancement of endogenous BDNF and subsequent
neurogenesis could partially underlie the neuroprotective effects of
progesterone.
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