title: The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat.
abstract: While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17β-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) were achieved 4h after onset of ischemia, and maintained until the end of the procedure (24h). Neurofunctional score and volume of the damaged brain regions were the main end points. At 24h after ischemia-reperfusion, neurofunctional examination of the animals did not show significant differences among the three experimental groups. By contrast, both E2- and BZA-treated groups showed significantly lower total infarct volumes, BZA acting mainly in the cortical region and E2 acting mainly at the subcortical level. Our results demonstrate that: (1) E2 at physiological plasma levels in female rats is neuroprotective in male rats when given at the acute stage of the ischemic challenge and (2) BZA at clinically relevant plasma levels mimics the neuroprotective action of E2 and could be, therefore, a candidate in stroke treatment.
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Castelló-Ruiz
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain. Electronic address: torregrosa_ger@gva.es.
authors.forename: Germán
authors.initials: G
authors.lastname: Torregrosa
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Burguete
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Miranda
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Centeno
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: Mikahela A
authors.initials: MA
authors.lastname: López-Morales
authors.affiliation: Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gasull
authors.affiliation: Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Unidad Mixta de Investigación Cerebrovascular (UMIC), Instituto de Investigación Sanitaria La Fe, Departamento de Fisiología, Universitat de València, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Alborch
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D004958:Estradiol / Q000627:therapeutic use; D006439:Hemodynamics; D007211:Indoles / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
chemical_list: D007211:Indoles; D018696:Neuroprotective Agents; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; C447119:bazedoxifene
keywords: 17β-Estradiol; Bazedoxifene; Ischemic stroke; Neuroprotection; Selective estrogen receptor modulators (SERMs)