Neuroprotection by a selective estrogen receptor beta 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 ERalpha 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 ERbeta.
Carswell
H V O
HV
Wellcome Surgical Institute & Hugh Fraser Neuroscience Labs., Division of Clinical Neuroscience, University of Glasgow, Glasgow G61 1QH, Scotland, UK. hvo1a@udcf.gla.ac.uk
Macrae
I M
IM
Gallagher
L
L
Harrop
E
E
Horsburgh
K J
KJ
D000818:Animals; D002421:Caudate Nucleus / Q000098:blood supply / Q000473:pathology; D004958:Estradiol / Q000378:metabolism; D047629:Estrogen Receptor beta; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047629:Estrogen Receptor beta; D018696:Neuroprotective Agents; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; C005557:propionitrile