title: Adaptive cerebral neovascularization in a model of type 2 diabetes: relevance to focal cerebral ischemia.
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.
  
  
  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.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Roshini
authors.initials: R
authors.lastname: Prakash
authors.forename: Aisha I
authors.initials: AI
authors.lastname: Kelly-Cobbs
authors.forename: Safia
authors.initials: S
authors.lastname: Ogbi
authors.forename: Anna
authors.initials: A
authors.lastname: Kozak
authors.forename: Azza B
authors.initials: AB
authors.lastname: El-Remessy
authors.forename: Derek A
authors.initials: DA
authors.lastname: Schreihofer
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology; D002536:Cerebral Arteries / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D002941:Circle of Willis / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D006442:Glycated Hemoglobin / Q000378:metabolism; D008297:Male; D008576:Meningeal Arteries / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D010841:Pia Mater / Q000098:blood supply; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin