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

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.