Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke

We previously observed that 17 beta-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. (C) 2012 Elsevier B.V. All rights reserved.