Mechanism of protection by soluble epoxide hydrolase inhibition in type 2 diabetic stroke

Kristen L. Zuloaga, Stephanie Krasnow, Xinxia Zhu, Wenri Zhang, Sari A. Jouihan, Robert Shangraw, Nabil Alkayed, Daniel Marks

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Inhibition of soluble epoxide hydrolase (sEH) is a potential target of therapy for ischemic injury. sEH metabolizes neuroprotective epoxyeicosatrienoic acids (EETs). We recently demonstrated that sEH inhibition reduces infarct size after middle cerebral artery occlusion (MCAO) in type 1 diabetic mice. We hypothesized that inhibition of sEH would protect against ischemic injury in type 2 diabetic mice. Type 2 diabetes was produced by combined high-fat diet, nicotinamide and streptozotocin in male mice. Diabetic and control mice were treated with vehicle or the sEH inhibitor t-AUCB then subjected to 60-min MCAO. Compared to chow-fed mice, high fat diet-fed mice exhibited an upregulation of sEH mRNA and protein in brain, but no differences in brain EETs levels were observed between groups. Type 2 diabetic mice had increased blood glucose levels at baseline and throughout ischemia, decreased laser-Doppler perfusion of the MCA territory after reperfusion, and sustained larger cortical infarcts compared to control mice. t-AUCB decreased fasting glucose levels at baseline and throughout ischemia, improved cortical perfusion after MCAO and significantly reduced infarct size in diabetic mice. We conclude that sEH inhibition, as a preventative treatment, improves glycemic status, post-ischemic reperfusion in the ischemic territory, and stroke outcome in type 2 diabetic mice.

Original languageEnglish (US)
Article numbere97529
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 13 2014

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epoxide hydrolase
Epoxide Hydrolases
stroke
Stroke
mice
infarction
Middle Cerebral Artery Infarction
Nutrition
arteries
Brain
High Fat Diet
Fats
high fat diet
ischemia
Reperfusion
Niacinamide
Ischemia
Perfusion
Streptozocin
Medical problems

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mechanism of protection by soluble epoxide hydrolase inhibition in type 2 diabetic stroke. / Zuloaga, Kristen L.; Krasnow, Stephanie; Zhu, Xinxia; Zhang, Wenri; Jouihan, Sari A.; Shangraw, Robert; Alkayed, Nabil; Marks, Daniel.

In: PLoS One, Vol. 9, No. 5, e97529, 13.05.2014.

Research output: Contribution to journalArticle

Zuloaga, Kristen L. ; Krasnow, Stephanie ; Zhu, Xinxia ; Zhang, Wenri ; Jouihan, Sari A. ; Shangraw, Robert ; Alkayed, Nabil ; Marks, Daniel. / Mechanism of protection by soluble epoxide hydrolase inhibition in type 2 diabetic stroke. In: PLoS One. 2014 ; Vol. 9, No. 5.
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