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

Authors

Dale Ding, Department of Neurosurgery, University of Virginia, Charlottesville, VAFollow
Robert M Starke, Department of Neurosurgery, University of Virginia, Charlottesville, VAFollow
Aaron S Dumont, Department of Neurosurgery, Tulane University, New Orleans, LAFollow
Gary K Owens, Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VAFollow
David M Hasan, Department of Neurosurgery, University of Iowa, Iowa City, IAFollow
Nohra Chalouhi, MD, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PAFollow
Ricky Medel, Department of Neurosurgery, Tulane University, New Orleans, LAFollow
Chih-Lung Lin, Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan ; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Document Type

Article

Publication Date

3-2014

Comments

This article is the final published version in BioMed Research International, Article number 727428

The published version is available at DOI: 10.1155/2014/727428. Copyright © Hindawi

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 17 β -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.

Recommended Citation

Ding, Dale; Starke, Robert M; Dumont, Aaron S; Owens, Gary K; Hasan, David M; Chalouhi, MD, Nohra; Medel, Ricky; and Lin, Chih-Lung, "Therapeutic Implications of Estrogen for Cerebral Vasospasm and Delayed Cerebral Ischemia Induced by Aneurysmal Subarachnoid Hemorrhage." (2014). Department of Neurosurgery Faculty Papers. Paper 57.
https://jdc.jefferson.edu/neurosurgeryfp/57

PubMed ID

24724095