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 acute ischemic stroke (AIS). The objective of the current study was to determine the effects of acute manipulation of potential targets for vascular protection (i.e., NFkB, peroxynitrite, and matrix metalloproteinases) on vascular injury and functional outcome in a diabetic model of cerebral ischemia. 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,a non-specific NFkB inhibitor curcumin, or a broad-spectrum matrix metalloproteinase (MMP) inhibitor minocycline at reperfusion. Post-stroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments 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. Uncovering underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.
- vascular protection
- Copyright © 2012, American Journal of Physiology - Heart and Circulatory Physiology