Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium

Janet L. Funk, Jennifer B. Frye, Grace Davis-Gorman, Allison L. Spera, Michael J. Bernas, Marlys H. Witte, Martin E. Weinand, Barbaba N. Timmermann, Paul F. Mcdonagh, Leslie Ritter

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Objective: We sought to test the hypothesis that turmeric-derived curcuminoids limit reperfusion brain injury in an experimental model of stroke via blockade of early microvascular inflammation during reperfusion. Methods: Male Sprague Dawley rats subjected to MCAO/R were treated with turmeric-derived curcuminoids (vs. vehicle) 1 hour prior to reperfusion (300 mg/kg ip). Neutrophil adhesion to the cerebral microcirculation and measures of neutrophil and endothelial activation were assayed during early reperfusion (0-4 hours); cerebral infarct size, edema, and neurological function were assessed at 24 hours. Curcuminoid effects on TNFα-stimulated human brain microvascular endothelial cell (HBMVEC) were assessed. Results: Early during reperfusion following MCAO, curcuminoid treatment decreased neutrophil rolling and adhesion to the cerebrovascular endothelium by 76% and 67% and prevented >50% of the fall in shear rate. The increased number and activation state (CD11b and ROS) of neutrophils were unchanged by curcuminoid treatment, while increased cerebral expression of TNFα and ICAM-1, a marker of endothelial activation, were blocked by >30%. Curcuminoids inhibited NF-κB activation and subsequent ICAM-1 gene expression in HBMVEC. Conclusion: Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.

Original languageEnglish (US)
Pages (from-to)544-554
Number of pages11
JournalMicrocirculation
Volume20
Issue number6
DOIs
StatePublished - Aug 1 2013

Keywords

  • Curcuminoids
  • Endothelium
  • Ischemia
  • Neutrophil
  • Reperfusion
  • Stroke

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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