naa a22 4500 510776078 CHVBK 20180411083230.0 cr unu---uuuuu 180411e20130801xx s 000 0 eng 10.1007/s12975-013-0253-6 doi (NATIONALLICENCE)springer-10.1007/s12975-013-0253-6 Oral Contraceptives and Nicotine Synergistically Exacerbate Cerebral Ischemic Injury in the Female Brain [Elektronische Daten] [Ami Raval, Raquel Borges-Garcia, Francisca Diaz, Thomas Sick, Helen Bramlett] Oral contraceptives (OC) and smoking-derived nicotine (N) are known to synergistically increase the risk and severity of cerebral ischemia in women. Although it has been known for some time that long-term use of OC and nicotine will have an increased risk of peripheral thrombus formation, little is known about how the combination of OC and nicotine increases severity of brain ischemia. Recent laboratory studies simulating the conditions of nicotine exposure produced by cigarette smoking and OC regimen of women in female rats confirms that the severity of ischemic hippocampal damage is far greater in female rats simultaneously exposed to OC than to nicotine alone. These studies also demonstrated that the concurrent exposure of OC and nicotine reduces endogenous 17β-estradiol levels and inhibits estrogen signaling in the brain of female rats. The endogenous 17β-estradiol plays a key role in cerebrovascular protection in women during their pre-menopausal life and loss of circulating estrogen at reproductive senescence increases both the incidence and severity of cerebrovascular diseases. Therefore, OC and nicotine induced severe post-ischemic damage might be a consequence of lack of estrogen signaling in the brain. In the present review we highlight possible mechanisms by which OC and nicotine inhibits estrogen signaling that could be responsible for severe ischemic damage in females. Springer Science+Business Media New York, 2013 Hippocampus nationallicence Estrogen receptors nationallicence Synaptic plasticity nationallicence Mitochondria nationallicence Complex IV nationallicence Raval Ami Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut Borges-Garcia Raquel Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut Diaz Francisca Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut Sick Thomas Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut Bramlett Helen Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/4(2013-08-01), 402-412 1868-4483 4:4<402 2013 4 12975 https://doi.org/10.1007/s12975-013-0253-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-013-0253-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raval Ami Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut NATIONALLICENCE 700 1- Borges-Garcia Raquel Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut NATIONALLICENCE 700 1- Diaz Francisca Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut NATIONALLICENCE 700 1- Sick Thomas Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut NATIONALLICENCE 700 1- Bramlett Helen Cerebral Vascular Disease Research Center, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Two Story Lab (TSL), Room # 230A, 1420 NW 9th Avenue, 33101, Miami, FL, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/4(2013-08-01), 402-412 1868-4483 4:4<402 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer