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

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.