Mechanism of Protection by Soluble Epoxide Hydrolase Inhibition in Type 2 Diabetic Stroke

Autor: Robert E. Shangraw, Kristen L. Zuloaga, Sari A. Jouihan, Daniel L. Marks, Nabil J. Alkayed, Wenri Zhang, Xinxia Zhu, Stephanie M. Krasnow
Rok vydání: 2014
Předmět:
Blood Glucose
Male
medicine.medical_treatment
lcsh:Medicine
Type 2 diabetes
Vascular Medicine
Benzoates
Mice
Endocrinology
0302 clinical medicine
Medicine and Health Sciences
Urea
lcsh:Science
Epoxide Hydrolases
0303 health sciences
Multidisciplinary
Brain
Infarction
Middle Cerebral Artery
3. Good health
Stroke
Neurology
cardiovascular system
Anatomy
Research Article
medicine.drug
Niacinamide
Epoxide hydrolase 2
medicine.medical_specialty
Cerebrovascular Diseases
Blotting
Western
Cardiology
Ischemia
Blood sugar
Diet
High-Fat
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Experimental
03 medical and health sciences
Internal medicine
Diabetes mellitus
medicine
Animals
cardiovascular diseases
Ischemic Stroke
030304 developmental biology
Diabetic Endocrinology
Analysis of Variance
Type 1 diabetes
business.industry
Insulin
lcsh:R
Biology and Life Sciences
medicine.disease
Streptozotocin
Surgery
Cardiovascular Anatomy
lcsh:Q
business
030217 neurology & neurosurgery
Zdroj: PLoS ONE, Vol 9, Iss 5, p e97529 (2014)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0097529
Popis: 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.
Databáze: OpenAIRE
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