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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 Cìoto-Kakizaki (GK) rats. The infarct volume, edema, hemorrhagic transformation, and shortterm neurological outcome were assessed after permanent middlecerebral artery occlusion (TVICAO).
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 occludili 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 lhe capillary level may contribute to smaller infarction, changes in the tight junction proteins may lead to lhe greater edema following cerebral ischemia in diabetes. Diabetes 59:228-235, 2010
Type 2 diabetic patients hold two- to fourfold higher risk for cerebrovascular disease and stroke (1,2), and 70% of patients with a recent stroke have overt diabetes or pre-diabetes distinguished by impaired fasting glucose or impaired glucose tolerance (3). However, the underlying basis of tins increased risk remains unclear. Diabetic vascular complications aie well studied in diabetic retinopathy, nephropathy, peripheral arterial disease, and coronary artery disease. However, diabetes-induced structural and functional changes in the cerebral vasculature are unknown.
It is becoming clear that the integrity of cerebral blood vessels is critical in the pathophysiology of stroke. While type 2 diabetes accounts lor -90-95% of all diagnosed cases of diabetes in adult patients, most of the experimental studies are focused on type 1 diabetes induced by streptozotocin (STZ) injection, which is associated with high-level and short-term elevations...