Adaptive cerebral neovascularization in a model of type 2 diabetes: relevance to focal cerebral ischemia.
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.


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 Goto-Kakizaki (GK) rats. The infarct volume, edema, hemorrhagic transformation, and short-term neurological outcome were assessed after permanent middle-cerebral artery occlusion (MCAO).


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 occludin 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 the capillary level may contribute to smaller infarction, changes in the tight junction proteins may lead to the greater edema following cerebral ischemia in diabetes.
Li
Weiguo
W
Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
Prakash
Roshini
R
Kelly-Cobbs
Aisha I
AI
Ogbi
Safia
S
Kozak
Anna
A
El-Remessy
Azza B
AB
Schreihofer
Derek A
DA
Fagan
Susan C
SC
Ergul
Adviye
A
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology; D002536:Cerebral Arteries / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D002941:Circle of Willis / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D006442:Glycated Hemoglobin / Q000378:metabolism; D008297:Male; D008576:Meningeal Arteries / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D010841:Pia Mater / Q000098:blood supply; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D006442:Glycated Hemoglobin