High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke

Randall S. Carpenter, Ifeanyi Iwuchukwu, Cyrus L. Hinkson, Sydney Reitz, Wonhee Lee, Ayaka Kukino, An Zhang, Martin Pike, Agnieszka A. Ardelt

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). Ktrans, a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke.

Original languageEnglish (US)
Pages (from-to)200-213
Number of pages14
JournalBrain Research
Volume1639
DOIs
StatePublished - May 15 2016

Fingerprint

Recovery of Function
Reperfusion
Estrogens
Stroke
Cerebrovascular Circulation
Middle Cerebral Artery Infarction
Brain
Therapeutics
Atrophy
Cysts
Corpus Striatum
Forelimb
Capillary Permeability
Ovariectomy
Reperfusion Injury
Wistar Rats
Estradiol
Placebos
Magnetic Resonance Imaging

Keywords

  • Angiogenesis
  • Estradiol
  • Functional recovery
  • Ischemic stroke
  • Magnetic resonance imaging
  • Neuroprotection

ASJC Scopus subject areas

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

Cite this

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke. / Carpenter, Randall S.; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L.; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin; Ardelt, Agnieszka A.

In: Brain Research, Vol. 1639, 15.05.2016, p. 200-213.

Research output: Contribution to journalArticle

Carpenter, Randall S. ; Iwuchukwu, Ifeanyi ; Hinkson, Cyrus L. ; Reitz, Sydney ; Lee, Wonhee ; Kukino, Ayaka ; Zhang, An ; Pike, Martin ; Ardelt, Agnieszka A. / High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke. In: Brain Research. 2016 ; Vol. 1639. pp. 200-213.
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