title: Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Nursing, University of Arizona, Tucson, Arizona, USA. lritter@nursing.arizona.edu
authors.forename: Leslie
authors.initials: L
authors.lastname: Ritter
authors.forename: Lisa
authors.initials: L
authors.lastname: Davidson
authors.forename: Melissa
authors.initials: M
authors.lastname: Henry
authors.forename: Grace
authors.initials: G
authors.lastname: Davis-Gorman
authors.forename: Helena
authors.initials: H
authors.lastname: Morrison
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Frye
authors.forename: Zoe
authors.initials: Z
authors.lastname: Cohen
authors.forename: Sierra
authors.initials: S
authors.lastname: Chandler
authors.forename: Paul
authors.initials: P
authors.lastname: McDonagh
authors.forename: Janet L
authors.initials: JL
authors.lastname: Funk
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000096:biosynthesis; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D019040:E-Selectin; D053583:Interleukin-1beta