title: Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke.
abstract: We previously observed that 17β-estradiol (E2) augments ischemic borderzone vascular density 10 days after focal cerebral ischemia-reperfusion in rats. We now evaluated the effect of E2 on vascular remodeling, lesional characteristics, and motor recovery up to 30 days after injury. Peri-lesional vascular density in tissue sections from rats treated with 0.72 mg E2 pellets was higher compared to 0.18 mg E2 pellets or placebo (P) pellets: vascular density index, 1.9 ± 0.2 (0.72 mg E2) vs. 1.4 ± 0.2 (0.18 mg E2) vs. 1.5 ± 0.4 (P), p=0.01. This was consistent with perfusion magnetic resonance imaging (MRI) measurements of lesional relative cerebral blood flow (rCBF): 1.89 ± 0.32 (0.72 mg E2) vs. 1.32 ± 0.19 (P), p=0.04. Post-ischemic angiogenesis occurred in P-treated as well as E2-treated rats. There was no treatment-related effect on lesional size, but lesional tissue was better preserved in E2-treated rats: cystic component as a % of total lesion, 30 ± 12 (0.72 mg E2) vs. 29 ± 17 (0.18 mg E2) vs. 61 ± 29 (P), p=0.008. Three weeks after right middle cerebral artery territory injury, rats treated with 0.72 mg E2 pellets used the left forelimb more than P-treated or 0.18 mg E2-treated rats: limb use asymmetry score, 0.09 ± 0.43 (0.72 mg E2) vs. 0.54 ± 0.12 (0.18 mg E2) vs. 0.54 ± 0.40 (P), p=0.05. We conclude that treatment with 0.72 mg E2 pellets beginning one week prior to ischemia/reperfusion and continuing through the one-month recovery period results in augmentation of lesional vascularity and perfusion, as well as improved motor recovery.
authors.affiliation: Department of Neurology, University of Chicago, Chicago, IL, USA. aardelt@neurology.bsd.uchicago.edu
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Ardelt
authors.forename: Randall S
authors.initials: RS
authors.lastname: Carpenter
authors.forename: Merryl R
authors.initials: MR
authors.lastname: Lobo
authors.forename: Huadong
authors.initials: H
authors.lastname: Zeng
authors.forename: Rajanikant B
authors.initials: RB
authors.lastname: Solanki
authors.forename: An
authors.initials: A
authors.lastname: Zhang
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulesza
authors.forename: Martin M
authors.initials: MM
authors.lastname: Pike
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004958:Estradiol