TY - JOUR
T1 - Neurovascular Injury in Acute Hyperglycemia and Diabetes
T2 - A Comparative Analysis in Experimental Stroke
AU - Elgebaly, Mostafa M.
AU - Ogbi, Safia
AU - Li, Weiguo
AU - Mezzetti, Erin M.
AU - Prakash, Roshini
AU - Johnson, Maribeth H.
AU - Bruno, Askiel
AU - Fagan, Susan C.
AU - Ergul, Adviye
N1 - Funding Information:
Acknowledgments The authors thank Anna Kozak and Dr. Cesar Borlongan for guidance with the MCAO surgery and Dr. Hazem Elewa and Dan Wiley for technical assistance with hemoglobin ELISA. This work was supported in part by grants from NIH [DK074385, NS054688] and American Heart Association Established Investigator Award [0740002 N] to A. E. and VA Merit Awards to S. C.F and A.E. AE is a research pharmacologist at the Charlie Norwood Veterans Affairs Medical Center in Augusta, Georgia.
PY - 2011/9
Y1 - 2011/9
N2 - Admission hyperglycemia impacts ischemic stroke deleteriously, but the relative role of acute hyperglycemia (HG) vs diabetes in the pathogenesis of this poor outcome is not clear. The study aims to determine the effect of acute HG on neurovascular outcomes of stroke under control and diabetic conditions. Moderate acute HG (140-200 mg/dl) was achieved by glucose injection before middle cerebral artery occlusion (MCAO) in control Wistar and diabetic Goto-Kakizaki rats. Following 3 h MCAO/21 h reperfusion, we measured infarct size, hemorrhagic transformation (HT) frequency, excess hemoglobin, neurobehavioral outcome, and MCA matrix metalloprotease activity. Infarct size was significantly smaller in diabetic rats. Moderate acute HG increased neuronal damage in diabetic but not in control rats. HT frequency and hemoglobin were significantly higher in diabetic rats. HG augmented vascular damage in control rats and had no additional effect on bleeding in diabetic rats. Neurological deficit was greater in diabetic rats and was worsened by HG. The finding that functional outcome is poorer in both acute HG and diabetes without a significant increase in infarct size suggests that amplified vascular damage contributes to neurological deficit in hyperglycemia. These results highlight the importance of vascular protection to improve neurological outcome in acute ischemic stroke.
AB - Admission hyperglycemia impacts ischemic stroke deleteriously, but the relative role of acute hyperglycemia (HG) vs diabetes in the pathogenesis of this poor outcome is not clear. The study aims to determine the effect of acute HG on neurovascular outcomes of stroke under control and diabetic conditions. Moderate acute HG (140-200 mg/dl) was achieved by glucose injection before middle cerebral artery occlusion (MCAO) in control Wistar and diabetic Goto-Kakizaki rats. Following 3 h MCAO/21 h reperfusion, we measured infarct size, hemorrhagic transformation (HT) frequency, excess hemoglobin, neurobehavioral outcome, and MCA matrix metalloprotease activity. Infarct size was significantly smaller in diabetic rats. Moderate acute HG increased neuronal damage in diabetic but not in control rats. HT frequency and hemoglobin were significantly higher in diabetic rats. HG augmented vascular damage in control rats and had no additional effect on bleeding in diabetic rats. Neurological deficit was greater in diabetic rats and was worsened by HG. The finding that functional outcome is poorer in both acute HG and diabetes without a significant increase in infarct size suggests that amplified vascular damage contributes to neurological deficit in hyperglycemia. These results highlight the importance of vascular protection to improve neurological outcome in acute ischemic stroke.
KW - Cerebral hemorrhage
KW - Hyperglycemia
KW - Ischemia-reperfusion Injury
KW - MMP-9 metalloproteinase
KW - Minocycline
KW - Type 2 diabetes mellitus
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U2 - 10.1007/s12975-011-0083-3
DO - 10.1007/s12975-011-0083-3
M3 - Article
C2 - 21909340
AN - SCOPUS:80052296902
SN - 1868-4483
VL - 2
SP - 391
EP - 398
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 3
ER -
