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BioMed Research International
Volume 2014, Article ID 727428, 9 pages
http://dx.doi.org/10.1155/2014/727428
Review Article

Therapeutic Implications of Estrogen for Cerebral Vasospasm and Delayed Cerebral Ischemia Induced by Aneurysmal Subarachnoid Hemorrhage

1Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA
2Department of Neurosurgery, Tulane University, New Orleans, LA 70112, USA
3Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
4Department of Neurosurgery, University of Iowa, Iowa City, IA 52242, USA
5Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19106, USA
6Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
7Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Received 23 December 2013; Accepted 21 January 2014; Published 2 March 2014

Academic Editor: John H. Zhang

Copyright © 2014 Dale Ding et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17β-estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal kinase activity, increasing neuroglobin levels, preventing SAH-induced suppression of the Akt signaling pathway, and upregulating the expression of adenosine A2a receptor. The net effect of E2 modulation of these various effectors is the promotion of neuronal survival, inhibition of apoptosis, and decreased oxidative damage and inflammation. E2 is a potentially potent therapeutic tool for improving outcomes related to post-SAH CV and DCI. However, clinical evidence supporting its benefits remains lacking. Given the promising preclinical data available, further studies utilizing E2 for the treatment of patients with ruptured intracranial aneurysms appear warranted.