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

AA Ardelt, RS Carpenter, MR Lobo, H Zeng… - Brain research, 2012 - Elsevier
AA Ardelt, RS Carpenter, MR Lobo, H Zeng, RB Solanki, A Zhang, P Kulesza, MM Pike
Brain research, 2012Elsevier
We previously observed that 17β-estradiol (E2) augments ischemic borderzone vascular
density 10days after focal cerebral ischemia–reperfusion in rats. We now evaluated the
effect of E2 on vascular remodeling, lesional characteristics, and motor recovery up to
30days 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 …
We previously observed that 17β-estradiol (E2) augments ischemic borderzone vascular density 10days after focal cerebral ischemia–reperfusion in rats. We now evaluated the effect of E2 on vascular remodeling, lesional characteristics, and motor recovery up to 30days after injury. Peri-lesional vascular density in tissue sections from rats treated with 0.72mg E2 pellets was higher compared to 0.18mg E2 pellets or placebo (P) pellets: vascular density index, 1.9±0.2 (0.72mg E2) vs. 1.4±0.2 (0.18mg 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 (0.72mg 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 (0.72mg E2) vs. 29±17 (0.18mg E2) vs. 61±29 (P), p=0.008. Three weeks after right middle cerebral artery territory injury, rats treated with 0.72mg E2 pellets used the left forelimb more than P-treated or 0.18mg E2-treated rats: limb use asymmetry score, 0.09±0.43 (0.72mg E2) vs. 0.54±0.12 (0.18mg E2) vs. 0.54±0.40 (P), p=0.05. We conclude that treatment with 0.72mg 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.
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