Adaptive Cerebral Neovascularization in a Model of Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 1; pp. 228 - 235
• Main Authors: Li, Weiguo, Prakash, Roshini, Kelly-Cobbs, Aisha I., Ogbi, Safia, Kozak, Anna, El-Remessy, Azza B., Schreihofer, Derek A., Fagan, Susan C., Ergul, Adviye
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2010
• Subjects: Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Medical sciences; Endocrinopathy; Type 2 diabetes; Central nervous system; Metabolic diseases; Models; Neovascularization; Encephalon
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-0902

Adaptive Cerebral Neovascularization in a Model of Type 2 Diabetes Relevance to Focal Cerebral Ischemia Weiguo Li 1 , Roshini Prakash 2 , Aisha I. Kelly-Cobbs 1 , Safia Ogbi 1 , Anna Kozak 2 , 3 , Azza B. El-Remessy 2 , 3 , Derek A. Schreihofer 1 , Susan C. Fagan 2 , 3 , 4 and Adviye Ergul 1 , 2 , 3 1 Department of Physiology, Medical College of Georgia, Augusta, Georgia; 2 Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, Georgia; 3 Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia; 4 Department of Neurology, Medical College of Georgia, Augusta, Georgia. Corresponding author: Adviye Ergul, aergul{at}mail.mcg.edu . Abstract OBJECTIVE The effect of diabetes on neovascularization varies between different organ systems. While excessive angiogenesis complicates diabetic retinopathy, impaired neovascularization contributes to coronary and peripheral complications of diabetes. However, how diabetes influences cerebral neovascularization is not clear. Our aim was to determine diabetes-mediated changes in the cerebrovasculature and its impact on the short-term outcome of cerebral ischemia. RESEARCH DESIGN AND METHODS Angiogenesis (capillary density) and arteriogenesis (number of collaterals and intratree anostomoses) were determined as indexes of neovascularization in the brain of control and type 2 diabetic Goto-Kakizaki (GK) rats. The infarct volume, edema, hemorrhagic transformation, and short-term neurological outcome were assessed after permanent middle–cerebral artery occlusion (MCAO). RESULTS The number of collaterals between middle and anterior cerebral arteries, the anastomoses within middle–cerebral artery trees, the vessel density, and the level of brain-derived neurotrophic factor were increased in diabetes. Cerebrovascular permeability, matrix metalloproteinase (MMP)-9 protein level, and total MMP activity were augmented while occludin was decreased in isolated cerebrovessels of the GK group. Following permanent MCAO, infarct size was smaller, edema was greater, and there was no macroscopic hemorrhagic transformation in GK rats. CONCLUSIONS The augmented neovascularization in the GK model includes both angiogenesis and arteriogenesis. While adaptive arteriogenesis of the pial vessels and angiogenesis at the capillary level may contribute to smaller infarction, changes in the tight junction proteins may lead to the greater edema following cerebral ischemia in diabetes. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received June 18, 2009. Accepted September 4, 2009. © 2010 American Diabetes Association