TY - JOUR
T1 - Adaptive cerebral neovascularization in a model of type 2 diabetes
T2 - Relevance to focal cerebral ischemia
AU - Li, Weiguo
AU - Prakash, Roshini
AU - Kelly-Cobbs, Aisha I.
AU - Ogbi, Safia
AU - Kozak, Anna
AU - El-Remessy, Azza B.
AU - Schreihofer, Derek A.
AU - Fagan, Susan C.
AU - Ergul, Adviye
PY - 2010/1
Y1 - 2010/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77449105172&partnerID=8YFLogxK
U2 - 10.2337/db09-0902
DO - 10.2337/db09-0902
M3 - Article
C2 - 19808897
AN - SCOPUS:77449105172
SN - 0012-1797
VL - 59
SP - 228
EP - 235
JO - Diabetes
JF - Diabetes
IS - 1
ER -