Exaggerated Neutrophil-Mediated Reperfusion Injury after Ischemic Stroke in a Rodent Model of Type 2 Diabetes

Leslie Ritter, Lisa Davidson, Melissa Henry, Grace Davis-Gorman, Helena Morrison, Jennifer B. Frye, Zoe Cohen, Sierra Chandler, Paul Mcdonagh, Janet L. Funk

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We tested the hypothesis that both chronic and acute inflammatory processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM. Materials and Methods: Twelve- to thirteen-week-old male Zucker Diabetic Fatty (ZDF) rats vs. Zucker Lean Controls (ZLC) rats were tested at baseline and after middle cerebral artery occlusion (ischemia) and reperfusion (I-R). Neutrophil adhesion to the cerebral microcirculation, neutrophil expression of CD11b, infarction size, edema, neurologic function, sICAM, and cerebral expression of neutrophil-endothelial inflammatory genes were measured. Results: At baseline, CD11b and sICAM were significantly increased in ZDF vs. ZLC animals (p<0.05). After I-R, significantly more neutrophil adhesion and cell aggregates were observed in ZDF vs. ZLC (p<0.05); infarction size, edema, and neurologic function were significantly worse in ZDF vs. ZLC (p<0.05). CD11b and sICAM-1 remained significantly increased in ZDFs (p<0.05), and cerebral expression of IL-1β, GRO/KC, E-selectin, and sICAM were significantly induced in ZDF, but not ZLC groups (p<0.05) after 2.5hours of reperfusion. Conclusion: Both sides of the neutrophil-endothelial interface appear to be primed prior to I-R, and remain significantly more activated during I-R in an experimental model of T2DM. Consequently, reperfusion injury appears to play a significant role in poor stroke outcome in T2DM.

Original languageEnglish (US)
Pages (from-to)552-561
Number of pages10
JournalMicrocirculation
Volume18
Issue number7
DOIs
StatePublished - Oct 1 2011

Keywords

  • Neutrophil
  • Reperfusion injury
  • Stroke
  • Type 2 diabetes
  • Zucker Diabetic Fatty rat

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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