Cerebral Neovascularization and Remodeling Patterns in Two Different Models of Type 2 Diabetes

Roshini Prakash, Maribeth H Johnson, Susan C. Fagan, Adviye Ergul

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 Leprdb/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 Leprdb/db mice. GK rats exhibited an increase in all of these parameters, which were prevented by glycemic control with metformin. In Leprdb/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.

Original languageEnglish (US)
Article numbere56264
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 18 2013

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Medical problems
angiogenesis
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Rats
glycemic control
Pathologic Neovascularization
rats
Fluorescein-5-isothiocyanate
Metformin
metformin
Diabetes Complications
Microvessels
Fluorescein
Hyperglycemia
Blood Vessels
mice
hyperglycemia
fluorescein
blood vessels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cerebral Neovascularization and Remodeling Patterns in Two Different Models of Type 2 Diabetes. / Prakash, Roshini; Johnson, Maribeth H; Fagan, Susan C.; Ergul, Adviye.

In: PloS one, Vol. 8, No. 2, e56264, 18.02.2013.

Research output: Contribution to journalArticle

Prakash, Roshini ; Johnson, Maribeth H ; Fagan, Susan C. ; Ergul, Adviye. / Cerebral Neovascularization and Remodeling Patterns in Two Different Models of Type 2 Diabetes. In: PloS one. 2013 ; Vol. 8, No. 2.
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