Neuroprotection by a selective oestrogen receptor {beta} agonist in a mouse model of global ischaemia

Hilary Carswell, I.M. Macrae, L. Gallagher, E. Harrop, K.J. Horsburgh

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125 Citations (Scopus)

Abstract

The present study employs selective estrogen receptor (ER) agonists to determine whether 17-estradiol-induced neuroprotection in global ischemia is receptor mediated and, if so, which subtype of receptor (ERα or ER) is predominantly responsible. Halothane-anesthetized female C57Bl/6J mice were ovariectomized, and osmotic minipumps containing ER agonist diarylpropiolnitrile (DPN) (8 mg·kg–1·day–1, n = 12) or vehicle (50% DMSO in 0.9% saline) (n = 9) or ERα agonist propyl pyrazole triol (PPT) (2 mg·kg–1·day–1, n = 13) or vehicle (50% DMSO in 0.9% saline) (n = 10) were implanted subcutaneously. One week later transient global ischemia was induced by bilateral carotid artery occlusion under halothane anesthesia, and the mice were perfusion fixed 72 h later. ER agonist DPN significantly reduced ischemic damage by 70% in the caudate nucleus and 55% in the CA1 region compared with vehicle controls (P < 0.05, Mann-Whitney U-statistic). In contrast, pretreatment with the ERα agonist PPT had no effect on the extent of neuronal damage compared with controls. The data indicate a significant estrogen receptor-mediated neuroprotection in a global cerebral ischemia model involving ER.
Original languageEnglish
Article numberIDS Number: 854IH
Pages (from-to)H1501-H1504
Number of pages5
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number4
Early online date20 May 2004
DOIs
Publication statusPublished - Oct 2004

Keywords

  • neuroprotector
  • oestrogen receptor
  • mouse model
  • global ischaemia

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