We evaluated long-term administration of estrogen after cardiac arrest and cardiopulmonary resuscitation (CA/CPR) on neurohistopathological and behavioral outcome. We also examined the effect of estrogen receptor (ER) stimulation using ER-α agonist propyl pyrazole triol (PPT) and ER-β agonist diarylpropionitrile (DPN) on neuronal survival after CA/CPR to determine whether possible neuroprotective effects of estrogen are ER-mediated. Male C57Bl/6 mice underwent 10 mins of CA/CPR and 3-day survival. In protocol 1, intravenous injection of vehicle (NaCl 0.9%) and 0.5 or 2.5 μg 17β-estradiol (E2 loading dose) was performed followed by subcutaneous implants containing vehicle (oil) or E2 (12.6 μg), according to a treatment group. In experimental protocol 2, mice were injected (intravenously) with the ER-α agonist PPT or ER-β agonist DPN followed by Alzet pump implants (subcutaneously) containing PPT (200 μg) or DPN (800 μg). Long-term E2 administration reduced neuronal injury in the striatum after administration of either loading dose (41%±19%, 35%±26% of injured neurons), as compared with vehicle (68%±7%, P<0.01), with no effect in the hippocampal CA1 field. In protocol 2, treatment with ER-β agonist DPN reduced neuronal injury in the striatum (51%±13% injured neurons) as compared with ER-α agonist PPT (68%±10%) and vehicle (69%±11%; P<0.01). Estrogen receptor-β agonist DPN reduced neuronal injury in the hippocampal CA1 field (29%±22% injured neurons) as compared with ER-α agonist PPT treatment (62%±33%; P<0.05). Injury was not different in hippocampal CA1 between vehicle and ER-α agonist-treated animals. We conclude that long-term E2 administration after CA/CPR is neuroprotective and that this effect is most likely mediated via ER-β.
- Cardiac arrest
- Cardiopulmonary resuscitation estradiol
- Erebral ischemia
- Estrogen receptor subtypes
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine