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Oral Contraceptives and Nicotine Synergistically Exacerbate Cerebral Ischemic Injury in the Female Brain

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Abstract

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.

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Acknowledgments

This study was supported by American Heart Association grants [11GRNT7370069, APR], Sex and Gender Influences on Addiction and Health: A Developmental Perspective [5 P50 DA024584-05], Stanley J. Glaser Foundation Research Grant, the Drs. Chantal and Peritz Scheinberg Research Fund to APR and the by National Institute of Health grant number GM101225 to FD.

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None.

Compliance with Ethics Requirements

Vertebrate animal use: In this review we have cited studies conducted at our lab. All institutional and national guidelines for the care and use of laboratory animals were followed at the time we conducted those studies.

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  1. 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, Miami, FL, 33101, USA

    Ami P. Raval, Raquel Borges-Garcia, Francisca Diaz, Thomas J. Sick & Helen Bramlett

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  1. Ami P. Raval
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  2. Raquel Borges-Garcia
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Correspondence to Ami P. Raval.

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Raval, A.P., Borges-Garcia, R., Diaz, F. et al. Oral Contraceptives and Nicotine Synergistically Exacerbate Cerebral Ischemic Injury in the Female Brain. Transl. Stroke Res. 4, 402–412 (2013). https://doi.org/10.1007/s12975-013-0253-6

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  • DOI: https://doi.org/10.1007/s12975-013-0253-6

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