title: Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice.
abstract: Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a 'cast' carotid device. In the second model, acute Evasin-3 treatment (5 minutes after cerebral ischemia onset) was assessed in mice subjected to transient left middle cerebral artery occlusion. Although CXCL1 and CXCL2 were upregulated in both atherosclerotic plaques and infarcted brain, only CXCL1 was detectable in serum. In carotid atherosclerosis, treatment with Evasin-3 was associated with reduction in intraplaque neutrophil and matrix metalloproteinase-9 content and weak increase in collagen as compared with Vehicle. In ischemic stroke, treatment with Evasin-3 was associated with reduction in ischemic brain neutrophil infiltration and protective oxidants. No other effects in clinical and histological outcomes were observed. We concluded that Evasin-3 treatment was associated with reduction in neutrophilic inflammation in both mouse models. However, Evasin-3 administration after cerebral ischemia onset failed to improve poststroke outcomes.
authors.affiliation: Division of Neurosurgery, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Copin
authors.forename: Rafaela F
authors.initials: RF
authors.lastname: da Silva
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Fraga-Silva
authors.forename: Luciano
authors.initials: L
authors.lastname: Capettini
authors.forename: Silvia
authors.initials: S
authors.lastname: Quintao
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.forename: Katia
authors.initials: K
authors.lastname: Galan
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burger
authors.forename: Vincent
authors.initials: V
authors.lastname: Braunersreuther
authors.forename: Karl
authors.initials: K
authors.lastname: Schaller
authors.forename: Maud
authors.initials: M
authors.lastname: Deruaz
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Stergiopulos
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
mesh_terms: D000818:Animals; D060829:Arthropod Proteins; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D020520:Brain Infarction / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001930:Brain Injuries / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D054360:Chemokine CXCL1 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D054387:Receptors, CXCR; D012471:Salivary Proteins and Peptides; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D060829:Arthropod Proteins; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C550668:Evasin-3 protein, tick; D054387:Receptors, CXCR; D012471:Salivary Proteins and Peptides