title: Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat.
abstract: The present study was undertaken to determine if estrogens protect female rats from the neurodegenerative effects of middle cerebral artery (MCA) occlusion. The rats were ovariectomized and 7 or 8 days later various estrogen preparations were administered before or after MCA occlusion. Pretreatment with 17beta-estradiol (17beta-E2) or a brain-targeted 17beta-E2 chemical delivery system (CDS) decreased mortality from 65% in ovariectomized rats to 22% in 17beta-E2-treated and 16% in 17beta-E2 CDS-treated rats. This marked reduction in mortality was accompanied by a reduction in the ischemic area of the brain from 25.6+/-5.7% in the ovariectomized rats to 9.8+/-4% and 9.1+/-4.2% in the 17beta-E2-implanted and the 17beta-E2 CDS-treated rats, respectively. Similarly, pretreatment with the presumed inactive estrogen, 17alpha-estradiol, reduced mortality from 36 to 0% and reduced the ischemic area by 55 to 81%. When administered 40 or 90 minutes after MCA occlusion, 17beta-E2 CDS reduced the area of ischemia by 45 to 90% or 31%, respectively. In summary, the present study provides the first evidence that estrogens exert neuroprotective effects in an animal model of ischemia and suggests that estrogens may be a useful therapy to protect neurons against the neurodegenerative effects of stroke.
authors.affiliation: Department of Pharmacodynamics and the Center for the Neurobiology of Aging, College of Pharmacy, University of Florida, Gainesville 32610, USA. simpkins@cop.health.ufl.edu
authors.forename: J W
authors.initials: JW
authors.lastname: Simpkins
authors.forename: G
authors.initials: G
authors.lastname: Rajakumar
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Zhang
authors.forename: C E
authors.initials: CE
authors.lastname: Simpkins
authors.forename: D
authors.initials: D
authors.lastname: Greenwald
authors.forename: C J
authors.initials: CJ
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Bodor
authors.forename: A L
authors.initials: AL
authors.lastname: Day
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D002536:Cerebral Arteries; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000502:physiology*; D005260:Female; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats
chemical_list: D004967:Estrogens; D004958:Estradiol