RT Journal Article SR Electronic T1 Combination of Hypoxia/Aglycemia Compromises In Vitro Blood-Brain Barrier Integrity JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 668 OP 675 VO 289 IS 2 A1 Thomas J. Abbruscato A1 Thomas P. Davis YR 1999 UL http://jpet.aspetjournals.org/content/289/2/668.abstract AB Increased cerebrovascular permeability is an important factor in the development of cerebral edema after stroke, implicating the blood-brain barrier (BBB) in the pathology of stroke. Present investigations modeled stroke at the level of the cerebral capillary endothelium by analyzing BBB permeability changes to the membrane-impermeant marker [14C]sucrose after hypoxia/aglycemia. Under hypoxia alone, long exposures (48 h) were necessary to result in a significant increase in permeability of bovine brain microvessel endothelial cells to [14C]sucrose. Hypoxia/aglycemia exposures resulted in a much shorter time (i.e., 1–3 h) required for a corresponding increase in permeability to [14C]sucrose. Statistically significant changes in basal permeability were observed between 3 and 6 h of hypoxia/aglycemia; however, 6 h of aglycemia alone had no significant effect on BBB permeability. Both rat astroglioma (C6) cells and C6 conditioned medium showed no improvements in barrier function measured by transendothelial cell resistance or permeability to [14C]sucrose. Changes in endothelial cell calcium flux may be responsible for the permeability change observed after both 48 h of hypoxia and 6 h of hypoxia/aglycemia because nifedipine (10 and 100 nM) and SKF 96365 (100 nM) decreased the permeability change. Immunocytochemical studies also revealed a change in the distribution of endothelial cell F-actin. This study provides evidence that the BBB is sensitive to short exposures of hypoxia/aglycemia and that changes in endothelial cell calcium flux may be responsible for structural and functional variations in the BBB during ischemic stress. The American Society for Pharmacology and Experimental Therapeutics