Amelioration of inflammation and cytotoxicity by dipyridamole in brain endothelial cells

Shuzhen Guo, Monique Stins, Mingming Ning, Eng H. Lo

Research output: Contribution to journalArticle

Abstract

Background: Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults. Methods: Human brain endothelial cells were grown in culture, and exposed to TNFα (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability. Results: Exposure of human brain endothelial cells to TNFα (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNFα did not alter PECAM-1. Dipyridamole (1-5 μM) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult. Conclusions: These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in stroke patients remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalCerebrovascular Diseases
Volume30
Issue number3
DOIs
StatePublished - Aug 1 2010

Keywords

  • Blood-brain barrier
  • Inflammation
  • Neurovascular
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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