期刊
DIABETES
卷 59, 期 1, 页码 228-235出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-0902
关键词
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资金
- National Institutes of Health [DK074385, NS054688]
- Philip Morris Inc
- Philip Morris International
- American Heart Association Established Investigator Award [0740002N]
- Department of Veterans Affairs Merit Award
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK074385] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS070239, R03NS054688] Funding Source: NIH RePORTER
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 awl 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. Diabetes 59:228-235, 2010
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