Abstract
Background
Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage
(SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis
after 17β-estradiol (E2) treatment is associated with an increase in phosphorylation
of Akt via estrogen receptor-α (ER-α) in rats.
Materials and methods
We examined the expression of phospho-Akt, ERα and ERβ, and apoptosis in cerebral
cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously
implanted other rats with a silicone rubber tube containing E2; they received daily
injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective
antagonist (methyl-piperidino-pyrazole), or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage.
Results
At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly
decreased and caspase-3 was significantly increased in the dentate gyrus. The cell
death assay revealed that DNA fragmentation was significantly increased in the dentate
gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole,
but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression
of the protein levels of phospho-Akt, ERα, ERβ, and caspase-3, and DNA fragmentation
after SAH.
Conclusions
The present study shows that a beneficial effect of E2 in attenuating SAH-induced
apoptosis is associated with activation of the expression of phospho-Akt and ERα,
and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the
dentate gyrus. These data support further the investigation of E2 in the treatment
of SAH in humans.
Keywords
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Article info
Publication history
Published online: February 11, 2013
Accepted:
January 17,
2013
Received in revised form:
January 12,
2013
Received:
July 25,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
