Estradiol protects against ischemic injury.
Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean+/-SD: oil = 241+/-88; low = 139+/-91; high = 132+/-88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.
Dubal
D B
DB
Department of Physiology, College of Medicine, University of Kentucky, Lexington 40536-0084, USA.
Kashon
M L
ML
Pettigrew
L C
LC
Ren
J M
JM
Finklestein
S P
SP
Rau
S W
SW
Wise
P M
PM
D000818:Animals; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D002544:Cerebral Infarction / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000503:physiopathology* / Q000517:prevention & control*; D017078:Laser-Doppler Flowmetry; D009928:Organ Specificity; D010052:Ovariectomy; D017698:Postmenopause; D051381:Rats; D017207:Rats, Sprague-Dawley
D004343:Drug Implants; D004958:Estradiol