title: Curcuminoids limit neutrophil-mediated reperfusion injury in experimental stroke by targeting the endothelium.
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.
  
  
  CONCLUSIONS
  Turmeric-derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.
authors: Department of Medicine, University of Arizona, Tucson, Arizona, USA. jfunk@u.arizona.edu
authors: Janet L
authors: JL
authors: Funk
authors: Jennifer B
authors: JB
authors: Frye
authors: Grace
authors: G
authors: Davis-Gorman
authors: Allison L
authors: AL
authors: Spera
authors: Michael J
authors: MJ
authors: Bernas
authors: Marlys H
authors: MH
authors: Witte
authors: Martin E
authors: ME
authors: Weinand
authors: Barbaba N
authors: BN
authors: Timmermann
authors: Paul F
authors: PF
authors: McDonagh
authors: Leslie
authors: L
authors: Ritter
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D039481:CD11b Antigen; C509295:ITGAM protein, human; D017382:Reactive Oxygen Species; D003474:Curcumin
keywords: curcuminoids; endothelium; ischemia; neutrophil; reperfusion; stroke