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

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Abstract
The present study employs selective estrogen receptor (ER) agonists to determine whether 17β-estradiol-induced neuroprotection in global ischemia is receptor mediated and, if so, which subtype of receptor (ERα or ERβ) is predominantly responsible. Halothane-anesthetized female C57Bl/6J mice were ovariectomized, and osmotic minipumps containing ERβ 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. ERβ 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.