Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes

Microcirculation. 2011 Oct;18(7):552-61. doi: 10.1111/j.1549-8719.2011.00115.x.

Abstract

Objective: 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 2.5 hours 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.

MeSH terms

  • Animals
  • CD11b Antigen / biosynthesis
  • Cell Adhesion
  • Chemokine CXCL1 / biosynthesis
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • E-Selectin / biosynthesis
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Gene Expression Regulation
  • Interleukin-1beta / biosynthesis
  • Neutrophils / metabolism*
  • Neutrophils / pathology
  • Rats
  • Rats, Zucker
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Stroke / metabolism*
  • Stroke / pathology

Substances

  • CD11b Antigen
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • E-Selectin
  • Interleukin-1beta