Abstract
The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17β-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.
Highlights
The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated
Sixty ovariectomized female rats were randomized into three groups differing in 17b-estradiol regimens, and transient focal cerebral ischemia was subsequently induced
All animals were subjected to a small functional testing battery, and three days after middle cerebral artery occlusion (MCAo) they were sacrificed for infarct size assessment
Summary
The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. The three most well-used administration methods for 17b-estradiol to rats were investigated, finding that the commercially available slow-release pellets (from the company Innovative Research of America) used produced exceptionally high serum levels of the hormone[9,10] These specific pellets had been used in our lab, but in all rat studies where estrogens had been reported neurotoxic, and the higher the 17b-estradiol dose in the pellets, the likelier the pellets were to augment the ischemic damage, which was shown in a meta-analysis[11]. The aim of the current study was to test whether a high-dose capsule (designed to produce approximately the same serum levels of 17b-estradiol as the earlier used neurotoxic pellets) would cause increased ischemic damage, while on the contrary a low-dose capsule would be neuroprotective. A possible mechanism for high-dose estrogens’ detrimental effects is preoperative weight loss, which was why the secondary aim of the study was to assess the impact of estrogen treatments on feeding behavior and body weight
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