Combination of hypoxia/aglycemia compromises in vitro blood-brain barrier integrity

Thomas J. Abbruscato, Thomas P. Davis

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Increased cerebrovascular permeability is an important factor n 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.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume289
Issue number2
StatePublished - May 1 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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