Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes

Weiguo Li, Aisha I. Kelly-Cobbs, Erin M. Mezzetti, Susan C. Fagan, Adviye Ergul

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Diabetes increases the risk of as well as poor outcome after stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media/lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeling on neurovascular damage following cerebral ischemic injury in GK rats 5 and 12 weeks after the onset of diabetes. The MCA structure, cerebral perfusion as well as infarct size, and hemorrhage were measured in control and diabetic rats subjected to transient MCA occlusion. M/L ratio was increased after 12 but not 5 weeks of diabetes. The baseline cerebral perfusion was lower and the infarct volume smaller in diabetic rats in both age groups. The incidence of hemorrhagic transformation was higher after 5 weeks of diabetes as compared to that after 12 weeks or in the control groups. These findings provide evidence that ET-1-mediated cerebrovascular remodeling does not worsen the neurovascular damage of ischemic brain injury in diabetes. It is possible that this early remodeling response is compensatory in nature to regulate vascular tone and integrity, especially when ischemia is layered on diabetic vascular disease.

Original languageEnglish (US)
Pages (from-to)788-795
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume88
Issue number8
DOIs
Publication statusPublished - Aug 1 2010

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Keywords

  • Cerebral ischemia
  • Diabetes
  • ET-1
  • Goto-Kakizaki rats
  • Remodeling

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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