Translational Stroke Research

, Volume 3, Issue 4, pp 500–507 | Cite as

GPER1/GPR30 Activation Improves Neuronal Survival Following Global Cerebral Ischemia Induced by Cardiac Arrest in Mice

  • Y. Kosaka
  • N. Quillinan
  • C. T. Bond
  • R. J. Traystman
  • P. D. Hurn
  • P. S. HersonEmail author
Original Article


Female sex steroids, particularly estrogens, contribute to the sexually dimorphic response observed in cerebral ischemic outcome, with females being relatively protected compared to males. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we previously demonstrated that estrogen neuroprotection is mediated in part by the estrogen receptor β, with no involvement of estrogen receptor α. In this study, we examined the neuroprotective effect of the novel estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30). Male mice administered with the GPR30 agonist G1 exhibited significantly reduced neuronal injury in the hippocampal CA1 region and striatum. The magnitude of neuroprotection observed in G1-treated mice was indistinguishable from estrogen-treated mice, implicating GPR30 in estrogen neuroprotection. Real-time quantitative RT-PCR indicates that G1 treatment increases expression of the neuroprotective ion channel, small-conductance calcium-activated potassium channel 2. We conclude that GPR30 agonists show promise in reducing brain injury following global cerebral ischemia.


Cardiac arrest GPR30/GPER1 SK2 Cerebral ischemia G1 



This work was supported by NIH R01NS058792, RO1NS046072, and RO1NR03521. This work was also supported by a Walter S. and Lucienne Driskill Foundation grant.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Y. Kosaka
    • 1
  • N. Quillinan
    • 1
    • 2
  • C. T. Bond
    • 3
  • R. J. Traystman
    • 2
    • 4
  • P. D. Hurn
    • 5
  • P. S. Herson
    • 1
    • 2
    Email author
  1. 1.Department of Anesthesiology and Perioperative MedicineOregon Health and Science UniversityPortlandUSA
  2. 2.Department of AnesthesiologyUniversity of Colorado DenverAuroraUSA
  3. 3.Vollum InstituteOregon Health and Science UniversityPortlandUSA
  4. 4.Department of PharmacologyUniversity of Colorado DenverAuroraUSA
  5. 5.Department of NeurobiologyUniversity of Texas at AustinAustinUSA

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