title: Cerebral neovascularization and remodeling patterns in two different models of type 2 diabetes.
abstract: We previously reported intense pial cerebral collateralization and arteriogenesis in a mild and lean model of type 2 diabetes (T2D), Goto-Kakizaki (GK) rats. Increased cerebral neovascularization differed regionally and was associated with poor vessel wall maturity. Building upon these findings, the goals of this study were to determine whether a) glycemic control prevents this erratic cerebral neovascularization in the GK model, and b) this pathological neovascularization pattern occurs in Lepr(db/db) model, which is the most commonly used model of T2D for studies involving cerebral complications of diabetes. Vascular volume, surface area and structural parameters including microvessel/macrovessel ratio, non-FITC (fluorescein) perfusing vessel abundance, vessel tortuosity, and branch density were measured by 3D reconstruction of FITC stained vasculature in GK rats or Lepr(db/db) mice. GK rats exhibited an increase in all of these parameters, which were prevented by glycemic control with metformin. In Lepr(db/db) mice, microvascular density was increased but there was no change in nonFITC-perfusing vessels. Increased PA branch density was associated with reduced branch diameter. These results suggest that T2D leads to cerebral neovascularization and remodeling but some structural characteristics of newly formed vessels differ between these models of T2D. The prevention of dysfunctional cerebral neovascularization by early glucose control suggests that hyperglycemia is a mediator of this response.
authors: Charlie Norwood Veterans Administration Medical Center, University of Georgia College of Pharmacy, Augusta, Georgia, United States of America.
authors: Roshini
authors: R
authors: Prakash
authors: Maribeth
authors: M
authors: Johnson
authors: Susan C
authors: SC
authors: Fagan
authors: Adviye
authors: A
authors: Ergul
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001786:Blood Glucose; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply; D009389:Neovascularization, Pathologic; D051381:Rats; D012171:Retinal Vessels / Q000473:pathology
chemical_list: D001786:Blood Glucose