Post-stroke periodic estrogen receptor-beta agonist improves cognition in aged female rats.

Autor: Pradhyumnan H; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Reddy V; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Bassett ZQ; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Patel SH; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Zhao W; Department of Biomedical Engineering, University of Miami, Coral Gables, FL, 33146, USA., Dave KR; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Perez-Pinzon MA; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Bramlett HM; Department of Neurological Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, 33136, USA., Raval AP; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, 33136, USA. Electronic address: araval@med.miami.edu.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2023 May; Vol. 165, pp. 105521. Date of Electronic Publication: 2023 Mar 17.
DOI: 10.1016/j.neuint.2023.105521
Abstrakt: Women have a higher risk of having an ischemic stroke and increased cognitive decline after stroke as compared to men. The female sex hormone 17β-estradiol (E2) is a potent neuro- and cognitive-protective agent. Periodic E2 or estrogen receptor subtype-beta (ER-β) agonist pre-treatments every 48 h before an ischemic episode ameliorated ischemic brain damage in young ovariectomized or reproductively senescent (RS) aged female rats. The current study aims to investigate the efficacy of post-stroke ER-β agonist treatments in reducing ischemic brain damage and cognitive deficits in RS female rats. Retired breeder (9-10 months) Sprague-Dawley female rats were considered RS after remaining in constant diestrus phase for more than a month. The RS rats were exposed to transient middle cerebral artery occlusion (tMCAO) for 90 min and treated with either ER-β agonist (beta 2, 3-bis(4-hydroxyphenyl) propionitrile; DPN; 1 mg/kg; s.c.) or DMSO vehicle at 4.5 h after induction of tMCAO. Subsequently, rats were treated with either ER-β agonist or DMSO vehicle every 48 h for ten injections. Forty-eight hours after the last treatment, animals were tested for contextual fear conditioning to measure post-stroke cognitive outcome. Neurobehavioral testing, infarct volume quantification, and hippocampal neuronal survival were employed to determine severity of stroke. Periodic post-stroke ER-β agonist treatment reduced infarct volume, improved recovery of cognitive capacity by increasing freezing in contextual fear conditioning, and decreased hippocampal neuronal death in RS female rats. These data suggest that periodic post-stroke ER-β agonist treatment to reduce stroke severity and improve post-stroke cognitive outcome in menopausal women has potential for future clinical investigation.
Competing Interests: Declaration of competing interest None.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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