Effects of combined oral conjugated estrogens and medroxyprogesterone acetate on brain infarction size after experimental stroke in rat.
The reason that estrogen is strongly protective in various estrogen-deficient animal models while seemingly detrimental in postmenopausal women remains unclear. It hypothesized that prolonged oral medroxyprogesterone (MPA) plus oral conjugated equine estrogens (CEE) diminishes estrogen ability to reduce stroke damage in the rodent stroke model. To test the hypothesis, we fed ovariectomized rats CEE or MPA, or a combination of CEE and MPA (CEP), before inducing 120 min of reversible focal stroke, using the intraluminal filament model. After 22 h reperfusion, the brains were harvested and infarction volumes were quantified. Treatment with CEE alone or with CEP reduced cortical infarction volume. However, CEP failed to provide ischemic protection in subcortical regions. It was concluded that CEE alone, or with CEP, is neuroprotective in the cortex, but interactive effects between the hormones may counteract CEE beneficial effects in subcortical brain regions.
Littleton-Kearney
Marguerite T
MT
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. mkearney@jhmi.edu
Klaus
Judy A
JA
Hurn
Patricia D
PD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008525:Medroxyprogesterone / Q000494:pharmacology*; D020768:Middle Cerebral Artery / Q000473:pathology; D017072:Neostriatum / Q000473:pathology; D018696:Neuroprotective Agents; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology; D020521:Stroke / Q000473:pathology*
D004966:Estrogens, Conjugated (USP); D018696:Neuroprotective Agents; D008525:Medroxyprogesterone