Neuroprotection and estrogen receptors

James W. Simpkins, Meharvan Singh, Courtney Brock, Anne M. Etgen

Research output: Contribution to journalReview articlepeer-review

78 Scopus citations


This review is intended to assess the state of current knowledge on the role of estrogen receptors (ERs) in the neuroprotective effects of estrogens in models for acute neuronal injury and death. We evaluate the overall evidence that estrogens are neuroprotective in acute injury and critically assess the role of ERα, ERβ, GPR 30, and nonreceptor-mediated mechanisms in these robust neuroprotective effects of this ovarian steroid hormone. We conclude that all three receptors, as well as nonreceptor-mediated mechanisms can be involved in neuroprotection, depending on the model used, the level of estrogen administrated, and the mode of administration of the steroid. Also, the signaling pathways used by both ER-dependent and ER-independent mechanisms to exert neuroprotection are considered. Finally, further studies that are needed to parse out the relative contribution of receptor versus nonreceptor-mediated signaling are discussed.

Original languageEnglish
Pages (from-to)119-130
Number of pages12
Issue number2
StatePublished - Sep 2012


  • Cerebral ischemia
  • Estradiol
  • Estrogen receptor alpha
  • Estrogen receptor beta
  • Estrogens
  • Neuroprotection
  • Nonfeminizing estrogens
  • Spinal cord injury
  • Stroke
  • Traumatic brain injury


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