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

Carswell, H. V. O., I. M. Macrae, L. Gallagher, E. Harrop, and K. J. Horsburgh. Neuroprotection by a selective estrogen receptor agonist in a mouse model of global ischemia. Am J Physiol Heart Circ Physiol 287: H1501–H1504, 2004. First published May 20, 2004; 10.1152/ajpheart.00227.2004.—The present study employs selective estrogen receptor (ER) agonists to determine whether 17 -estradiolinduced neuroprotection in global ischemia is receptor mediated and, if so, which subtype of receptor (ER 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 , n 12) or vehicle (50% DMSO in 0.9% saline) (n 9) or ER agonist propyl pyrazole triol (PPT) (2 mg kg 1 day , 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 ER 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 .