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17β-Estradiol attenuates secondary injury through activation of Akt signaling via estrogen receptor alpha in rat brain following subarachnoid hemorrhage

  • Cheng-Hsing Kao
    Affiliations
    Center for General Education, Southern Taiwan University of Technology, Tainan, Taiwan

    Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan
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  • Chih-Zen Chang
    Affiliations
    Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, Republic of China
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  • Yu-Feng Su
    Affiliations
    Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Yee-Jean Tsai
    Affiliations
    Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Kao-Ping Chang
    Affiliations
    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Division of Plastic and Reconstructive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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  • Tzu-Kang Lin
    Affiliations
    Department of Neurosurgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
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  • Shiuh-Lin Hwang
    Affiliations
    Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chih-Lung Lin
    Correspondence
    Corresponding author. Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100 Tz-you 1st Road, Koahsiung City 807, Taiwan. Tel.: +886 7 3121101 extension 5880; fax: +886 7 3215049.
    Affiliations
    Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Published:February 11, 2013DOI:https://doi.org/10.1016/j.jss.2013.01.033

      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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