Abstract TP256: Targets of Vascular Protection in Acute Ischemic Stroke Differ in Type 2 Diabetes
Background: Hemorrhagic transformation (HT) is an important complication of acute ischemic stroke particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator (tPA), the only approved drug for the treatment of AIS. The objective of the current study was to determine the effects of acute inhibition of the mediators of HT (i.e., NFkB, peroxynitrite, and matrix metalloproteinases) on vascular injury and functional outcome in a diabetic model of cerebral ischemia.
Methods: Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of peroxynitrite decomposition catalyst FeTPPs, non-specific NFkB inhibitor curcumin, or broad-spectrum matrix metalloproteinase (MMP) inhibitor minocycline at reperfusion. Post-stroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated.
Results: All therapies reduced MMP-9 and HT in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment as indicated by beam-walk performance, modified Bederson scores and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline.
Conclusion: Uncovering underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. Table 1. Summary of experimental stroke data. SE are shown in parentheses. a p<0.05 vs. untreated control, b p<0.05 vs. untreated, c p<0.05 vs. untreated diabetes, d p<0.001 vs. untreated control, e p<0.01 vs. untreated control, *All values in this data set were below detection.
- © 2012 by American Heart Association, Inc.