Neuroprotective actions of estradiol and novel estrogen analogs in ischemia: Translational implications

Anne M. Etgen, Teresa Jover-Mengual, R. Suzanne Zukin

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


This review highlights our investigations into the neuroprotective efficacy of estradiol and other estrogenic agents in a clinically relevant animal model of transient global ischemia, which causes selective, delayed death of hippocampal CA1 neurons and associated cognitive deficits. We find that estradiol rescues a significant number of CA1 pyramidal neurons that would otherwise die in response to global ischemia, and this is true when hormone is provided as a long-term pretreatment at physiological doses or as an acute treatment at the time of reperfusion. In addition to enhancing neuronal survival, both forms of estradiol treatment induce measurable cognitive benefit in young animals. Moreover, estradiol and estrogen analogs that do not bind classical nuclear estrogen receptors retain their neuroprotective efficacy in middle-aged females deprived of ovarian hormones for a prolonged duration (8. weeks). Thus, non-feminizing estrogens may represent a new therapeutic approach for treating the neuronal damage associated with global ischemia.

Original languageEnglish (US)
Pages (from-to)336-352
Number of pages17
JournalFrontiers in Neuroendocrinology
Issue number3
StatePublished - Aug 2011


  • Apoptosis
  • CREB
  • Estradiol
  • Estrogen receptor
  • GPR30
  • Global ischemia
  • Hippocampus
  • Insulin-like growth factor-1
  • Neuroprotection
  • Stroke

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems


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