title: Progesterone Changes VEGF and BDNF Expression and Promotes Neurogenesis After Ischemic Stroke.
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.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, People's Republic of China. chaojzzu@126.com.|Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21205, USA. chaojzzu@126.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, People's Republic of China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zuo
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, People's Republic of China.
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400044, China.
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21205, USA. jwang79@jhmi.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
keywords: Brain-derived neurotrophic factor; Cerebral ischemia; Neurogenesis; Progesterone; Vascular endothelial growth factor