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Ischemic injury, hemorrhagic transformation and plasma MMP‐9 profile in experimental diabetes vs. hyperglycemia
Author(s) -
Elgebaly Mostafa,
Mezzetti Erin M,
Fagan Susan C,
Ergul Adviye
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb41
Subject(s) - medicine , diabetes mellitus , stroke (engine) , basal (medicine) , endocrinology , zymography , ischemia , occlusion , reperfusion injury , matrix metalloproteinase , mechanical engineering , engineering
Diabetes increases stroke risk. We recently showed cerebrovascular remodeling associated with higher matrix metalloproteinase (MMP) activity and increased hemorrhagic transformation (HT) following 3 h middle cerebral artery occlusion /21 h reperfusion in Type 2 diabetes. Plasma MMP‐9 may be predictive of HT following tPA treatment in stroke. Thus, the goals of this study were to measure plasma MMP‐9 before and after stroke in control and Type 2 diabetic Goto‐Kakizaki (GK) rats and in acutely hyperglycemic rats during stroke. The hypothesis was that baseline plasma MMP‐9 activity is higher in GKs and is further elevated after ischemia. Plasma MMP‐9 activity was determined at baseline and at sacrifice after 3/21 MCAO/reperfusion by zymography. Basal MMP‐9 activity was higher in GKs (11.2 ± 4.1 vs. 0.7 ± 0.3, n=6, p<0.001). MCAO/reperfusion significantly increased plasma MMP‐9 in control, diabetic and acute hyperglycemia rats (103 ± 23.2, 113 ± 15, 124 ± 9, respectively, n=3‐6, p<0.0001 vs. baseline) but there was no difference between groups. Infarct size was smaller in GK (11 ± 4%, n=3, p<0.01) vs. control (42 ± 6%, n=4) and hyperglycemic (47 ± 6%, n=4) rats. Control animals had no HT yet there was macroscopic bleeding in GK and hyperglycemic rats. These results suggest that 24 h plasma MMP‐9 levels are not associated with higher bleeding in diabetic and hyperglycemic rats and earlier time points merit evaluation.