Effects of 17beta-estradiol on blood-brain barrier disruption during focal cerebral ischemia in younger and older rats.
This study was performed to compare the effects of 17beta-estradiol on blood-brain barrier disruption in focal cerebral ischemia between younger and older rats. Younger (three-month-old) and older (24-month-old) ovariectomized female Fischer 344 rats were studied. In one half of each age group, a 500 microg 17beta-estradiol 21-day release pellet and in another half, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion, the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to examine the degree of blood-brain barrier disruption. In all four groups, the Ki in the ischemic cortex was higher than in the corresponding contralateral cortex. There was no significant difference in the Ki in both cortices among the groups. The volume of dextran distribution of the ischemic cortex was only greater than in the corresponding contralateral cortex in the older 17beta-estradiol-treated group, and the volume of that group was greater than the younger 17beta-estradiol-treated group (4.00 +/- 1.29 VS. 2.13 +/- 0.88 ml/100 g). After analyzing the difference in Ki between the ischemic cortex and the contralateral cortex in each animal, the difference was significantly greater in the older 17beta-estradiol-treated rats than the older vehicle-treated rats (3.40 +/- 2.10 VS. 1.26 +/- 1.44 microl/g/min). In the younger rats, however, 17beta-estradiol did not significantly affect the difference. Our data showed that 17beta-estradiol treatment failed to attenuate the BBB disruption in the cerebral ischemic cortex in the older or younger Fischer 344 rats. However, our data also suggest the possibility that 17beta-estradiol could aggravate the BBB disruption in older rats.
Chi
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Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-1977, USA. chi@umdnj.edu
Hunter
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Liu
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D000375:Aging; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy*; D002199:Capillary Permeability; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D003911:Dextrans / Q000493:pharmacokinetics; D004343:Drug Implants; D004958:Estradiol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000621:Aminoisobutyric Acids; D003911:Dextrans; D004343:Drug Implants; C100049:2-aminoisobutyric acid; D004958:Estradiol