Abstract TP436: Dysfunctional Cerebral Neovascularization And Remodeling Patterns In Obese And Lean Models Of Type 2 Diabetes
We previously reported intense pial cerebral collateralization and arteriogenesis in a mild and lean model of type 2 diabetes, Goto-Kakizaki (GK) rats. Further 3-dimensional fluroscein (FITC) imaging studies revealed regional differences in increased cerebral neovascularization which was associated with poor vessel wall maturity. Building upon these findings, the goals of this study were a) to compare and contrast this pathological neovascularization pattern in db/db mice and GK models of diabetes, and b) determine the effect of glycemic control on erratic cerebral neovascularization. Total vascular volume, density and surface area as well as structural parameters including microvessel/macrovessel ratio, non-FITC perfusing vessel abundance, penetrating arteriole (PA) branching density and diameter, and tortuosity were measured by 3 dimensional reconstruction of FITC stained vasculature using Z-stacked images obtained with confocal microscopy. Lean GK rats exhibited an increase in both micro and macrovessel density, non-perfusing vessel abundance, branch density, diameter and tortuosity. Glycemic control with metformin prevented these changes. Obese db/db mice, on the other hand, showed an increase in only microvascular density but this was not associated with an increase in non-FITC perfusing vessels. PA branch density was higher than controls but branch diameter was reduced. Diabetes also promoted astrogliosis. These results suggests that type 2 diabetes leads to cerebral neovascularization and remodeling but structural characteristics of newly formed vessels differ between lean and obese models that have mild or severe hyperglycemia, respectively. The prevention of dysfunctional cerebral neovascularization by early glucose control suggests that hyperglycemia is a mediator of this response. N=4-8 * p≤ 0.05, ** p≤ 0.005 *** 0.0005
- © 2012 by American Heart Association, Inc.