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Periodic Estrogen Receptor-Beta Activation: A Novel Approach to Prevent Ischemic Brain Damage.
MedLine Citation:
PMID:  24906488     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In women, the risk for cerebral ischemia climbs rapidly after menopause. At menopause, production of ovarian hormones; i.e., progesterone and estrogen, slowly diminishes. Estrogen has been suggested to confer natural protection to premenopausal women from ischemic stroke and some of its debilitating consequences. This notion is also strongly supported by laboratory studies showing that a continuous chronic 17β-estradiol (E2; a potent estrogen) regimen protects brain from ischemic injury. However, concerns regarding the safety of the continuous intake of E2 were raised by the failed translation to the clinic. Recent studies demonstrated that repetitive periodic E2 pretreatments, in contrast to continuous E2 treatment, provided neuroprotection against cerebral ischemia in ovariectomized rats. Periodic E2 pretreatment protects hippocampal neurons through activation of estrogen receptor subtype beta (ER-β). Apart from neuroprotection, periodic activation of ER-β in ovariectomized rats significantly improves hippocampus-dependent learning and memory. Difficulties in learning and memory loss are the major consequence of ischemic brain damage. Periodic ER-β agonist pretreatment may provide pharmacological access to a protective state against ischemic stroke and its debilitating consequences. The use of ER-β-selective agonists constitutes a safer target for future research than ER-α agonist or E2, inasmuch as it lacks the ability to stimulate the proliferation of breast or endometrial tissue. In this review, we highlight ER-β signaling as a guide for future translational research to reduce cognitive decline and cerebral ischemia incidents/impact in post-menopausal women, while avoiding the side effects produced by chronic E2 treatment.
Authors:
Lauren Cue; Francisca Diaz; Karoline J Briegel; Hersila H Patel; Ami P Raval
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-7
Journal Detail:
Title:  Neurochemical research     Volume:  -     ISSN:  1573-6903     ISO Abbreviation:  Neurochem. Res.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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