Neurovascular Injury in Acute Hyperglycemia and Diabetes: a Comparative Analysis in Experimental Stroke
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ORIGINAL ARTICLE
Neurovascular Injury in Acute Hyperglycemia and Diabetes: a Comparative Analysis in Experimental Stroke Mostafa M. Elgebaly & Safia Ogbi & Weiguo Li & Erin M. Mezzetti & Roshini Prakash & Maribeth H. Johnson & Askiel Bruno & Susan C. Fagan & Adviye Ergul
Received: 17 January 2011 / Revised: 28 March 2011 / Accepted: 17 April 2011 / Published online: 3 May 2011 # Springer Science+Business Media, LLC 2011
Abstract Admission hyperglycemia impacts ischemic stroke deleteriously, but the relative role of acute hyperglycemia (HG) vs diabetes in the pathogenesis of this poor outcome is not clear. The study aims to determine the effect of acute HG on neurovascular outcomes of stroke under control and diabetic conditions. Moderate acute HG (140–200 mg/dl) was achieved by glucose injection before middle cerebral artery occlusion (MCAO) in control Wistar and diabetic GotoKakizaki rats. Following 3 h MCAO/21 h reperfusion, we measured infarct size, hemorrhagic transformation (HT) frequency, excess hemoglobin, neurobehavioral outcome, and MCA matrix metalloprotease activity. Infarct size was significantly smaller in diabetic rats. Moderate acute HG M. M. Elgebaly : R. Prakash : S. C. Fagan : A. Ergul Program in Clinical and Experimental Therapeutics, Department of Clinical and Administrative Pharmacy, College of Pharmacy, University of Georgia, HM-1200, Augusta, GA 30912, USA S. Ogbi : W. Li : E. M. Mezzetti : A. Ergul (*) Department of Physiology, Georgia Health Sciences University, 1120 15th St, CA2094, Augusta, GA 30912, USA e-mail: [email protected] M. H. Johnson Department of Biostatistics, Georgia Health Sciences University, 1120 15th St, CA2094, Augusta, GA 30912, USA A. Bruno Department of Neurology, Georgia Health Sciences University, 1120 15th St, CA2094, Augusta, GA 30912, USA S. C. Fagan : A. Ergul Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30912, USA
increased neuronal damage in diabetic but not in control rats. HT frequency and hemoglobin were significantly higher in diabetic rats. HG augmented vascular damage in control rats and had no additional effect on bleeding in diabetic rats. Neurological deficit was greater in diabetic rats and was worsened by HG. The finding that functional outcome is poorer in both acute HG and diabetes without a significant increase in infarct size suggests that amplified vascular damage contributes to neurological deficit in hyperglycemia. These results highlight the importance of vascular protection to improve neurological outcome in acute ischemic stroke. Keywords MMP-9 metalloproteinase . Minocycline . Cerebral hemorrhage . Ischemia–reperfusion Injury . Type 2 diabetes mellitus . Hyperglycemia
Introduction Ischemic stroke is a leading cause of death and disability in the USA, and diabetes is the most rapidly increasing risk factor for stroke [1]. Stroke risk in patients with diabetes is 2–6-folds higher than age-matched controls [1]. The shortand long-term functional outcomes are worse, and mortality is greater in stroke patients with dia
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