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

Brain Res. 2012 Jun 21;1461:76-86. doi: 10.1016/j.brainres.2012.04.024. Epub 2012 Apr 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / physiopathology
  • Cerebrovascular Circulation / drug effects*
  • Cerebrovascular Circulation / physiology
  • Disease Models, Animal*
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Female
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Time Factors
  • Treatment Outcome

Substances

  • Estradiol