Increased expression of icam-1 during reoxygenation in brain endothelial cells

David C Hess, Wei Zhao, James Edwin Carroll, Michael McEachin, Kenny Buchanan

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Abstract

Background and PurposeThrombolysis is a promising therapy for acute ischemic stroke. However, there is evidence that neutrophils may physically plug cerebral microvessels on reperfusion, preventing the full benefit of thrombolysis. We undertook this study to determine whether there was increased endothelial expression of the intercellular adhesion molecule-1 (ICAM-1) gene during hypoxia-reoxygenation. MethodsWe isolated and cultured human brain microvas-cular endothelial cells and subjected them to hypoxia (Po2<10 mm Hg) in an anaerobic chamber followed by variable periods of reoxygenation. ResultsTwenty-hour periods of hypoxia did not lead to endothelial cytotoxicity as measured by a chromium-release assay. By Northern blot analysis, ICAM-1 mRNA transcripts were dramatically increased at 4 hours of reoxygenation but fell toward baseline (normoxia) by 12 and 24 hours. Hypoxia alone did not lead to an increase in mRNA levels. Western blot analysis showed an increased expression of ICAM-1 at 4,12, and 24 hours of reoxygenation. The 4-hour increase in mRNA levels was not attenuated by pretreatment with 100 μmol/L allopurinol but was reduced by 30% with the addition of 20 mmol/L N-acetyl-L-cysteine at the time of reoxygenation and completely prevented by pretreatment with N-acetyi-L-cysteine. ConclusionsHypoxia-reoxygenation leads to an increase in ICAM mRNA levels that peaks at 4 hours in human brain microvascular endothelial cells. Pretreatment with N-acetyl-L-cysteine can completely block the increase in ICAM-1 mRNA levels.

Original languageEnglish (US)
Pages (from-to)1463-1467
Number of pages5
JournalStroke
Volume25
Issue number7
DOIs
StatePublished - Jul 1994

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Keywords

  • Cerebral circulation
  • Endothelium
  • Hypoxia
  • Neutrophils

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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