Neuroprotection by a selective estrogen receptor β agonist in a mouse model of global ischemia

The present study employs selective estrogen receptor (ER) agonists to determine whether 17beta- estradiol-induced neuroprotection in global ischemia is receptor mediated and, if so, which subtype of receptor (ERalpha or ERbeta) is predominantly responsible. Halothane-anesthetized female C57Bl/6J mice were ovariectomized, and osmotic minipumps containing ERbeta agonist diarylpropiolnitrile (DPN) (8 mg . kg(-1) . day(-1), n = 12) or vehicle (50% DMSO in 0.9% saline) ( n = 9) or ERalpha 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. ERbeta 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 ERβ.