Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes.
BACKGROUND
Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.


METHODS
Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome.


RESULTS
Infarct size was significantly smaller in GK rats (10 +/- 2 vs 30 +/- 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 +/- 0.01 vs 1.34 +/- 0.06, P < 0.001) indicative of changes in vessel architecture.


CONCLUSIONS
These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.
Ergul
Adviye
A
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, USA. aergul@mcg.edu
Elgebaly
Mostafa M
MM
Middlemore
Mary-Louise
ML
Li
Weiguo
W
Elewa
Hazem
H
Switzer
Jeffrey A
JA
Hall
Christiana
C
Kozak
Anna
A
Fagan
Susan C
SC
D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D020520:Brain Infarction / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology*; D020300:Intracranial Hemorrhages / Q000209:etiology* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009460:Neurologic Examination / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D012720:Severity of Illness Index
D001786:Blood Glucose; D020778:Matrix Metalloproteinase 2