Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia

Wenri Zhang, Jeffrey Iliff, Caitlyn J. Campbell, Ruikang K. Wang, Patricia D. Hurn, Nabil Alkayed

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sEHKO) mice. Male, female, and ovariectomized female WT and sEHKO mice were subjected to 2-h middle cerebral artery occlusion (MCAO) and infarct size was measured at 24 h of reperfusion. Laser-Doppler cortical perfusion during MCAO was compared among groups and differences in cortical blood flow rates were confirmed using in vivo quantitative optical microangiography. Cerebrovascular expression and activity of sEH and plasma 14,15-DHET were lower in WT female than male mice, and blood flow during MCAO was higher and infarct size was smaller in WT female compared with male mice. Sex differences in cerebral blood flow and ischemic damage were abolished after ovariectomy and were absent in sEHKO mice. We conclude that sEH is an important mechanism underlying sex-linked differences in blood flow and brain damage after cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)1475-1481
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Epoxide Hydrolases
Brain Ischemia
Blood Vessels
Middle Cerebral Artery Infarction
Knockout Mice
Sex Characteristics
Cerebrovascular Circulation
Eicosanoids
Brain
Ovariectomy
Hydrolases
Vasodilator Agents
Reperfusion
Estrogens
Lasers
Perfusion
Acids
Enzymes

Keywords

  • EETs
  • Epoxide hydrolase
  • Estrogen
  • Ischemia
  • Optical imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia. / Zhang, Wenri; Iliff, Jeffrey; Campbell, Caitlyn J.; Wang, Ruikang K.; Hurn, Patricia D.; Alkayed, Nabil.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 8, 08.2009, p. 1475-1481.

Research output: Contribution to journalArticle

Zhang, Wenri ; Iliff, Jeffrey ; Campbell, Caitlyn J. ; Wang, Ruikang K. ; Hurn, Patricia D. ; Alkayed, Nabil. / Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia. In: Journal of Cerebral Blood Flow and Metabolism. 2009 ; Vol. 29, No. 8. pp. 1475-1481.
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