Abstract 111: Cerebrovascular Remodeling In Diabetes: Relevance To Stroke
Background: Diabetes is a major risk factor of stroke leading to the development of both large artery and lacunar infarcts associated with increased bleeding, and neurological and functional disability. We previously reported enhanced cerebral arteriogenesis in a mild and lean model of Type 2 diabetes. Here we hypothesize that cerebral neovascularization is regulated in a spatial manner in diabetes and vascular endothelial growth factor (VEGF) and peroxynitrite signaling are the underlying key regulators of increased remodeling.
Methods: Neovascularization was assessed from brain, skeletal muscles and retina of control Wistar and diabetic Goto-Kakizaki rats. 3-dimensional reconstruction of the FITC stained vasculature were obtained by confocal microscopy and stereological parameters like vascular volume, density and surface area were measured. Unperfused vasculature was measured by immunostaining with Isolectin B4. Pericyte coverage was determined by nuclear staining (DAPI). VEGF and tyrosine nitration were evaluated by immunoblot and slot blot.
Results: There was a progressive increase (rostral to caudal) in both cortical and striatal angiogenic parameters in the diabetic group. Cortical vascular density was more pronounced than the striatum in the diabetic group. Difference between FITC and Isolectin co-staining revealed that unperfused new vessels were prominent in the diabetic striatum. Endothelial cell number was markedly increased and pericyte/endothelial cell ratio indicating vascular maturity was significantly decreased in diabetes. Peripheral vascularization was impaired while increased in the retina. VEGF-A was greater in the microvessels but not macrovessels or brain homogenates devoid of vessels in diabetic animals. Diabetic microvessels also exhibited greater tyrosine nitration.
Conclusion: Diabetes uniquely mediates cerebral neovascularization while regresses the peripheral vasculature. There exist spatial and regional differences in the diabetic brain that have relevance to neurovascular injury in stroke. Excessive neovascularization, a large pool of unperfused microvessels and reduced pericytes compromise the blood brain barrier and lead to increased bleeding during reperfusion injury in diabetes. N=4-10 *p≤ 0.05, ** p≤ 0.005
- © 2012 by American Heart Association, Inc.