title: Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats.
abstract: The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.
authors.affiliation: Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Edvin
authors.initials: E
authors.lastname: Ingberg
authors.affiliation: Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Elvar
authors.initials: E
authors.lastname: Theodorsson
authors.affiliation: Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Division of Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland.
authors.forename: Annette
authors.initials: A
authors.lastname: Theodorsson
authors.affiliation: Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden.|School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Jakob O
authors.initials: JO
authors.lastname: Ström
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004958:Estradiol
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