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

Publication ,  Journal Article
Ding, D; Starke, RM; Dumont, AS; Owens, GK; Hasan, DM; Chalouhi, N; Medel, R; Lin, C-L
Published in: Biomed Res Int
2014

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.

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Published In

Biomed Res Int

DOI

EISSN

2314-6141

Publication Date

2014

Volume

2014

Start / End Page

727428

Location

United States

Related Subject Headings

  • Vasospasm, Intracranial
  • Vasodilation
  • Subarachnoid Hemorrhage
  • Neuroprotective Agents
  • Nerve Tissue Proteins
  • Humans
  • Estrogens
  • Estradiol
  • Brain Ischemia
  • Animals
 

Citation

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Ding, D., Starke, R. M., Dumont, A. S., Owens, G. K., Hasan, D. M., Chalouhi, N., … Lin, C.-L. (2014). Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage. Biomed Res Int, 2014, 727428. https://doi.org/10.1155/2014/727428
Ding, Dale, Robert M. Starke, Aaron S. Dumont, Gary K. Owens, David M. Hasan, Nohra Chalouhi, Ricky Medel, and Chih-Lung Lin. “Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage.Biomed Res Int 2014 (2014): 727428. https://doi.org/10.1155/2014/727428.
Ding D, Starke RM, Dumont AS, Owens GK, Hasan DM, Chalouhi N, et al. Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage. Biomed Res Int. 2014;2014:727428.
Ding, Dale, et al. “Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage.Biomed Res Int, vol. 2014, 2014, p. 727428. Pubmed, doi:10.1155/2014/727428.
Ding D, Starke RM, Dumont AS, Owens GK, Hasan DM, Chalouhi N, Medel R, Lin C-L. Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage. Biomed Res Int. 2014;2014:727428.

Published In

Biomed Res Int

DOI

EISSN

2314-6141

Publication Date

2014

Volume

2014

Start / End Page

727428

Location

United States

Related Subject Headings

  • Vasospasm, Intracranial
  • Vasodilation
  • Subarachnoid Hemorrhage
  • Neuroprotective Agents
  • Nerve Tissue Proteins
  • Humans
  • Estrogens
  • Estradiol
  • Brain Ischemia
  • Animals