Neurovascular injury in acute hyperglycemia and diabetes: A comparative analysis in experimental stroke

Admission hyperglycemia impacts ischemic stroke deleteriously but the relative role of acute hyperglycemia (HG) versus diabetes in the pathogenesis of this poor outcome is not clear.

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 (GK) rats. Following 3 h MCAO/21 h reperfusion, we measured infarct size, hemorrhagic transformation (HT) frequency, excess hemoglobin, neurobehavioral outcome and plasma and MCA matrix metalloprotease (MMP) 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. Baseline plasma MMP-9 activity was significantly higher in diabetic rats. HG increased MMP-9 activity in control and 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.