title: Post-stroke estradiol treatment enhances neurogenesis in the subventricular zone of rats after permanent focal cerebral ischemia.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, 157# West 5 Road, Xi'an, Shaanxi 710004, China.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Lei
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Qi
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000089662:Doublecortin Protein; D004958:Estradiol / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol