Effect of sustained-mild and transient-severe hyperglycemia on ischemia-induced blood-brain barrier opening

J Cereb Blood Flow Metab. 2007 Sep;27(9):1573-82. doi: 10.1038/sj.jcbfm.9600454. Epub 2007 Feb 7.

Abstract

The purpose of this study was to examine what levels of hyperglycemia cause blood-brain barrier (BBB) disruption during permanent and transient middle cerebral artery occlusion in the rat and when the adverse effects of hyperglycemia occur. Cerebrovascular function was assessed by measuring the influx rate constant (K(i)) for (3)H-inulin and by measuring cerebral plasma ((14)C-inulin) and (51)Cr-labeled red blood cell (RBC) volume. Different glucose protocols were used to produce mild sustained hyperglycemia (blood glucose approximately 150 mg/dL) or transient-severe hyperglycemia (with a spike in blood glucose of approximately 400 mg/dL). As expected, transient-severe hyperglycemia at the time of occlusion induced marked BBB disruption in animals undergoing 2 h of ischemia with 2 h of reperfusion (25-fold increase in permeability compared with the contralateral core). However, the mild hyperglycemia model induced similar disruption. Similarly, after permanent occlusion, both hyperglycemia models enhanced disruption and they both produced marked ( approximately 50%) reductions in cerebral plasma volume. Apparent cerebral RBC volume also decreased when measured during the final 5 mins of 2 h of ischemia with transient-severe hyperglycemia. However, there was no decrease if the (51)Cr-labeled RBCs were circulated for the whole 2 h, indicating RBC trapping. The spike in blood glucose in the severe hyperglycemia model was used to examine when hyperglycemia induced BBB disruption. Hyperglycemia shortly after occlusion caused severe disruption. In contrast, hyperglycemia after 90 mins of occlusion caused little disruption. These results suggest that mild hyperglycemia has a profound effect on BBB function and that very early correction of hyperglycemia is necessary to prevent adverse effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiopathology*
  • Brain / blood supply*
  • Brain Ischemia / complications
  • Brain Ischemia / physiopathology*
  • Capillary Permeability / physiology*
  • Cerebrovascular Circulation / physiology
  • Hyperglycemia / complications
  • Hyperglycemia / physiopathology*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Rats
  • Rats, Sprague-Dawley