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 Pike

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalBrain Research
Volume1461
DOIs
StatePublished - Jun 21 2012

Fingerprint

Estradiol
Stroke
Blood Vessels
Reperfusion
Cerebrovascular Circulation
Forelimb
Magnetic Resonance Angiography
Middle Cerebral Artery
Wounds and Injuries
Brain Ischemia
Vascular Remodeling
Ischemia
Extremities
Perfusion
Placebos
Therapeutics

Keywords

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

ASJC Scopus subject areas

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

Cite this

Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke. / Ardelt, Agnieszka A.; Carpenter, Randall S.; Lobo, Merryl R.; Zeng, Huadong; Solanki, Rajanikant B.; Zhang, An; Kulesza, Piotr; Pike, Martin.

In: Brain Research, Vol. 1461, 21.06.2012, p. 76-86.

Research output: Contribution to journalArticle

Ardelt, Agnieszka A. ; Carpenter, Randall S. ; Lobo, Merryl R. ; Zeng, Huadong ; Solanki, Rajanikant B. ; Zhang, An ; Kulesza, Piotr ; Pike, Martin. / Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke. In: Brain Research. 2012 ; Vol. 1461. pp. 76-86.
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AU - Solanki, Rajanikant B.

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AU - Kulesza, Piotr

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