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

Agnieszka A. Ardelt, Randall S. Carpenter, Merryl R. Lobo, Huadong Zeng, Rajanikant B. Solanki, An Zhang, Piotr Kulesza, Martin M. Pike

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalBrain research
StatePublished - Jun 21 2012


  • Angiogenesis
  • Cerebral ischemia
  • Estradiol
  • Functional recovery
  • Magnetic resonance imaging
  • Middle cerebral artery occlusion
  • Neurorepair
  • Rat
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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