Progesterone Changes VEGF and BDNF Expression and Promotes Neurogenesis After Ischemic Stroke

And we will never understand  how this works until we actually get a stroke strategy and sponsor research to answer these simple questions. But this won't occur because we have NO stroke strategy or stroke leadership in any part of stroke and this will fall thru the cracks.
http://link.springer.com/article/10.1007/s12035-015-9651-y

• Chao Jiang 
• , Fangfang Zuo
• , Yuejuan Wang
• , Hong Lu
• , Qingwu Yang
• , Jian Wang 

$39.95 / €34.95 / £29.95 *

* Final gross prices may vary according to local VAT.

Get Access

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.

Keywords

Brain-derived neurotrophic factor Cerebral ischemia Neurogenesis Progesterone Vascular endothelial growth factor

Highlights

• Rats underwent a permanent middle cerebral artery occlusion model of stroke.

• Progesterone increased BDNF but decreased VEGF on day 3 post-occlusion.

• Progesterone reduced brain edema.

• Progesterone increased neurogenesis and improved functional outcome.

• Progesterone treatment provides a therapeutic effect after ischemic stroke.