Curcuminoids Limit Neutrophil‐Mediated Reperfusion Injury in Experimental Stroke by Targeting the Endothelium. (9th August 2013)

• Record Type: Journal Article
• Authors: Funk, Janet L.; Frye, Jennifer B.; Davis‐Gorman, Grace; Spera, Allison L.; Bernas, Michael J.; Witte, Marlys H.; Weinand, Martin E.; Timmermann, Barbaba N.; McDonagh, Paul F.; Ritter, Leslie
• Is Part Of: Microcirculation. Volume 20:Number 6(2013:Aug.)
• Page Start: 544
• Page End: 554
• Publication Date: 2013-08-09
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12054
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12054-abs-0001"> <title>Abstract</title> <sec id="micc12054-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="micc12054-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="micc12054-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="micc12054-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Turmeric‐derived curcuminoids limit reperfusion injury in stroke by preventing neutrophil adhesion to the cerebrovascular microcirculation and improving shear rate by targeting the endothelium.</p> </sec> </abstract>