Chronic nicotine exposure inhibits 17β-estradiol-mediated protection of the hippocampal CA1 region against cerebral ischemia in female rats

Ami P. Raval, Anoop Bhatt, Isabel Saul

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19 Scopus citations


Nicotine addiction in women increases the risk of ischemic stroke. Importantly, women who smoke and use hormone replacement therapy/oral contraceptives greatly increase their risk of coronary heart disease and ischemic stroke as compared to nonsmoking women who use occasionally oral contraceptives. Nicotine addiction disturbs the normal periodicity of the menstrual cycle and induces early onset of menopause in women; however, the mechanism of the synergistic effects of nicotine and sex hormones on cerebrovascular health is not clearly understood. In the current study based on a rat model of global cerebral ischemia, our goals are (1) to determine whether chronic nicotine exposure abrogates beneficial effects of estrogen on hippocampal neurons subjected to ischemia, and (2) to determine whether nicotine exposure antagonizes estrogen signaling by reducing the availability of estrogen receptor(s). To test the effects of chronic nicotine exposure, normally cycling or ovariectomized rats were injected with nicotine daily for 15 days. To investigate the efficacy of estrogen treatment, nicotine-exposed ovariectomized rats were injected with a bolus of 17β-estradiol and 48 h later ischemia was induced. Our results demonstrated that chronic nicotine exposure followed by ischemic insult at the proestrus stage of the estrous cycle showed that only 14% of normal neurons remained compared to the non-nicotine-treated group (p < 0.05). Similarly, a bolus of 17β-estradiol to nicotine-treated ovariectomized rats showed only 26% of normal neurons remaining as against 47% in the non-nicotine-treated group. Nicotine exposure decreased ERβ but not ERα protein levels in the hippocampus, suggesting a role for ERβ in increased post-ischemic neurodegeneration from nicotine exposure.

Original languageEnglish (US)
Pages (from-to)65-69
Number of pages5
JournalNeuroscience Letters
Issue number2
StatePublished - Jul 17 2009



  • Estrogen receptors
  • Estrous cycle
  • Hippocampus
  • Neuroprotection
  • Smoking

ASJC Scopus subject areas

  • Neuroscience(all)

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