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Different methods for administering 17beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage
Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-6681-0546
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.
2010 (English)In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 11, article id 39Article in journal (Refereed) Published
Abstract [en]

Background: Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17beta-estradiol administration; home-made silastic capsules instead of commercial slow-release 17beta-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17beta-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.

Results: In contrast to our earlier results using the commercial pellets, the group receiving 17b-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean ± SEM: 3.85 ± 0.70% versus 7.15 ± 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17b-estradiol was administered only during the two weeks before or the three days immediately after MCAo.

Conclusions: The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2010. Vol. 11, article id 39
National Category
Medical and Health Sciences Neurology
Identifiers
URN: urn:nbn:se:oru:diva-48111DOI: 10.1186/1471-2202-11-39ISI: 000276444500001PubMedID: 20236508Scopus ID: 2-s2.0-77951178010OAI: oai:DiVA.org:oru-48111DiVA, id: diva2:901436
Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2017-11-30Bibliographically approved

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Ström, Jakob O.

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