Adaptive cerebral neovascularization in a model of type 2 diabetes

Relevance to focal cerebral ischemia

Weiguo Li, Roshini Prakash, Aisha I. Kelly-Cobbs, Safia Ogbi, Anna Kozak, Azza B. El-Remessy, Derek A. Schreihofer, Susan C. Fagan, Adviye Ergul

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalDiabetes
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2010

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Brain Ischemia
Type 2 Diabetes Mellitus
Edema
Middle Cerebral Artery Infarction
Middle Cerebral Artery
Occludin
Tight Junction Proteins
Anterior Cerebral Artery
Brain-Derived Neurotrophic Factor
Matrix Metalloproteinase 9
Diabetic Retinopathy
Diabetes Complications
Matrix Metalloproteinases
Infarction
Permeability
Research Design
Brain
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Li, W., Prakash, R., Kelly-Cobbs, A. I., Ogbi, S., Kozak, A., El-Remessy, A. B., ... Ergul, A. (2010). Adaptive cerebral neovascularization in a model of type 2 diabetes: Relevance to focal cerebral ischemia. Diabetes, 59(1), 228-235. https://doi.org/10.2337/db09-0902

Adaptive cerebral neovascularization in a model of type 2 diabetes : Relevance to focal cerebral ischemia. / Li, Weiguo; Prakash, Roshini; Kelly-Cobbs, Aisha I.; Ogbi, Safia; Kozak, Anna; El-Remessy, Azza B.; Schreihofer, Derek A.; Fagan, Susan C.; Ergul, Adviye.

In: Diabetes, Vol. 59, No. 1, 01.01.2010, p. 228-235.

Research output: Contribution to journalArticle

Li, W, Prakash, R, Kelly-Cobbs, AI, Ogbi, S, Kozak, A, El-Remessy, AB, Schreihofer, DA, Fagan, SC & Ergul, A 2010, 'Adaptive cerebral neovascularization in a model of type 2 diabetes: Relevance to focal cerebral ischemia', Diabetes, vol. 59, no. 1, pp. 228-235. https://doi.org/10.2337/db09-0902
Li W, Prakash R, Kelly-Cobbs AI, Ogbi S, Kozak A, El-Remessy AB et al. Adaptive cerebral neovascularization in a model of type 2 diabetes: Relevance to focal cerebral ischemia. Diabetes. 2010 Jan 1;59(1):228-235. https://doi.org/10.2337/db09-0902
Li, Weiguo ; Prakash, Roshini ; Kelly-Cobbs, Aisha I. ; Ogbi, Safia ; Kozak, Anna ; El-Remessy, Azza B. ; Schreihofer, Derek A. ; Fagan, Susan C. ; Ergul, Adviye. / Adaptive cerebral neovascularization in a model of type 2 diabetes : Relevance to focal cerebral ischemia. In: Diabetes. 2010 ; Vol. 59, No. 1. pp. 228-235.
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AU - Kozak, Anna

AU - El-Remessy, Azza B.

AU - Schreihofer, Derek A.

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N2 - 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.

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