title: Post-stroke treatment with 17β-estradiol exerts neuroprotective effects in both normotensive and hypertensive rats.
abstract: Although ischemic stroke is a major cause of death worldwide and the predominant cause of acquired disability, the only effective drug therapy that has been developed thus far is reperfusion by tissue plasminogen activator. Since most patients do not qualify for this treatment, new methods have to be developed. It is well known that estradiol (E2) exerts neuroprotective effects in different models of cerebral ischemia, but post-stroke treatment after an acute stroke has hardly been investigated. As many patients with an acute ischemic stroke have arterial hypertension, it is also of interest to evaluate the influence of this co-morbidity on the treatment efficacy of E2. The effects of E2administered 30min after a transient middle cerebral artery occlusion (tMCAO) induced by an intracerebral injection of endothelin-1 were assessed in male normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Treatment with E2reduced infarct size in both WKY and SHRs and decreased the number of degenerating neurons, indicating that acute treatment with E2is indeed neuroprotective. To address the role of glia in neuroprotection, the effects of E2on the activation of microglia and astrocytes was determined. It appeared that E2had no effect on microglial activation, but reduced the activation of astrocytes in SHRs but not in the normotensive controls. We conclude that post-stroke E2treatment in both normotensive and hypertensive rats is neuroprotective. Although the presence of hypertension changed the astrocytic response to E2, it did not affect treatment efficacy.
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stoop
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Deborah
authors.initials: D
authors.lastname: De Geyter
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Verachtert
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium; Department of Pharmacology and Cardiovascular Center, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussel, Belgium; Department of Cardiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Sofie
authors.initials: S
authors.lastname: Brouwers
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Peggy
authors.initials: P
authors.lastname: Verdood
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium; Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium; Department of Neurology, University Medical Center Groningen, 9700 Groningen, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: De Keyser
authors.affiliation: Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: Ron.Kooijman@vub.ac.be.
authors.forename: Ron
authors.initials: R
authors.lastname: Kooijman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications*; D008297:Male; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000150:complications / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D004958:Estradiol
keywords: estradiol; hypertension; neuroprotection; rat; stroke