Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage

Dale Ding; Robert M Starke; Aaron S Dumont; Gary K Owens; David M Hasan; Nohra Chalouhi; Ricky Medel; Chih-Lung Lin

doi:10.1155/2014/727428

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Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage

Journal article

Open access

Peer reviewed

Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage

Dale Ding, Robert M Starke, Aaron S Dumont, Gary K Owens, David M Hasan, Nohra Chalouhi, Ricky Medel and Chih-Lung Lin

BioMed research international, Vol.2014, pp.727428-9

2014

DOI: 10.1155/2014/727428

PMCID: PMC3958795

PMID: 24724095

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https://doi.org/10.1155/2014/727428View

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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.

Neuroprotective Agents - therapeutic use

Estradiol - therapeutic use

Humans

Brain Ischemia - metabolism

Subarachnoid Hemorrhage - pathology

Vasodilation

Estrogens - therapeutic use

Subarachnoid Hemorrhage - metabolism

Nerve Tissue Proteins - metabolism

Animals

Brain Ischemia - drug therapy

Brain Ischemia - pathology

Vasospasm, Intracranial - metabolism

Subarachnoid Hemorrhage - drug therapy

Vasospasm, Intracranial - drug therapy

Vasospasm, Intracranial - pathology

Details

Title: Subtitle: Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage
Creators: Dale Ding - Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA
Robert M Starke - Department of Neurosurgery, University of Virginia, Charlottesville, VA 22908, USA
Aaron S Dumont - Department of Neurosurgery, Tulane University, New Orleans, LA 70112, USA
Gary K Owens - Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA
David M Hasan - Department of Neurosurgery, University of Iowa, Iowa City, IA 52242, USA
Nohra Chalouhi - Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19106, USA
Ricky Medel - Department of Neurosurgery, Tulane University, New Orleans, LA 70112, USA
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
Resource Type: Journal article
Publication Details: BioMed research international, Vol.2014, pp.727428-9
DOI: 10.1155/2014/727428
PMID: 24724095
PMCID: PMC3958795
NLM abbreviation: Biomed Res Int
ISSN: 2314-6133
eISSN: 2314-6141
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS P30 CA044579 / NCI NIH HHS 1K08NS067072 / NINDS NIH HHS K08 NS067072 / NINDS NIH HHS
Language: English
Date published: 2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurosurgery; Otolaryngology
Record Identifier: 9984040292802771

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