title: Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.
abstract: Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] 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 the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation 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 the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies.
authors: Department of Physiology, Georgia Regents University Augusta, Augusta, GA 30912, USA.
authors: Aisha I
authors: AI
authors: Kelly-Cobbs
authors: Roshini
authors: R
authors: Prakash
authors: Weiguo
authors: W
authors: Li
authors: Bindu
authors: B
authors: Pillai
authors: Sherif
authors: S
authors: Hafez
authors: Maha
authors: M
authors: Coucha
authors: Maribeth H
authors: MH
authors: Johnson
authors: Safia N
authors: SN
authors: Ogbi
authors: Susan C
authors: SC
authors: Fagan
authors: Adviye
authors: A
authors: Ergul
mesh_terms: D000818:Animals; D003474:Curcumin / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D004487:Edema / Q000188:drug therapy; D006470:Hemorrhage / Q000188:drug therapy; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008124:Locomotion; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D008665:Metalloporphyrins / Q000627:therapeutic use*; D008911:Minocycline / Q000627:therapeutic use*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
chemical_list: C466420:5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride; D061965:Matrix Metalloproteinase Inhibitors; D008665:Metalloporphyrins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D030421:Peroxynitrous Acid; D020780:Matrix Metalloproteinase 9; D008911:Minocycline; D003474:Curcumin