Estrogen preconditioning: A promising strategy to reduce inflammation in the ischemic brain.
Extracellular vesicles
Inflammasome
Menopause
NOD-like receptors (NLRs)
Reproductively senescent
Journal
Conditioning medicine
ISSN: 2577-3240
Titre abrégé: Cond Med
Pays: United States
ID NLM: 101718750
Informations de publication
Date de publication:
2019
2019
Historique:
entrez:
4
7
2020
pubmed:
1
1
2019
medline:
1
1
2019
Statut:
ppublish
Résumé
During the premenopausal phase of a woman's life, estrogen naturally protects against ischemic brain damage and its debilitating consequence of cognitive decline. However, the decline in estrogen at menopause exponentially increases a women's risk for cerebral ischemia and its severity. Supplementation of estrogen during menopause is the most logical solution to abate this increased risk for cerebral ischemia; however, continuous therapy has proven to be contraindicative. Studies from our laboratory over the past decade have shown that a single bolus or long-term periodic 17β-estradiol treatment(s) two days prior to ischemia mimics ischemic preconditioning-conferred protection of the brain in ovariectomized or reproductively senescent female rats. These studies also demonstrated that 17β-estradiol-induced preconditioning (EPC) requires estrogen receptor (ER)-subtype beta (ER-β) activation. ER-β is expressed throughout the brain, including in the hippocampus, which plays a key role in learning and memory. Because periodic activation of ER-β mitigates post-ischemic cognitive decline in ovariectomized female rats, it can be surmised that EPC has the potential to reduce post-ischemic damage and cognitive decline in females. Estrogens are key anti-inflammatory agents; therefore this review discusses the effects of EPC on the inflammasome. Furthermore, as we now clearly know, the brain acts differently in males and females. Indeed, neurodegenerative diseases, including cerebral ischemia, and pharmacological drugs affect males and females in different ways. Thus, inasmuch as the National Institutes of Health and the Stroke Treatment Academic Industry Roundtable (STAIR) consortium mandate inclusion of female experimental animals, this review also discusses the need to close the gap in our knowledge in future studies of EPC in female animal models of cerebral ischemia.
Types de publication
Journal Article
Langues
eng
Pagination
106-113Subventions
Organisme : NINDS NIH HHS
ID : R01 NS034773
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS045676
Pays : United States
Déclaration de conflit d'intérêts
Conflicts of interest Helen M. Bramlett and Juan Pablo de Rivero Vaccari are co-founders and managing members of InflamaCORE, LLC, a company dedicated to developing therapies and diagnostic tools focusing on the inflammasome. Helen M. Bramlett and Juan Pablo de Rivero Vaccari are Scientific Advisory Board Members of Variant Pharmaceuticals, Inc. All other authors declare that there are no conflicts of interest.
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