title: Ultra-sensitive molecular MRI of vascular cell adhesion molecule-1 reveals a dynamic inflammatory penumbra after strokes.
abstract: OBJECTIVE
  Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method.
  
  
  METHODS
  We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke.
  
  
  RESULTS
  Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1-enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra.
  
  
  CONCLUSIONS
  MPIOs-αVCAM-1-enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale (INSERM) U919 Serine Protease and Pathophysiology of the Neurovascular Unit, University Caen Basse-Normandie, GIP Cyceron, Bd Becquerel, BP5229, Caen, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
authors.forename: Axel
authors.initials: A
authors.lastname: Montagne
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Marcos-Contreras
authors.forename: Audrey
authors.initials: A
authors.lastname: Le Béhot
authors.forename: Eric
authors.initials: E
authors.lastname: Maubert
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000818:Animals; D005290:Ferric Compounds; D007089:Image Enhancement / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D019010:Vascular Cell Adhesion Molecule-1; C000499:ferric oxide
keywords: MRI; VCAM; neuroinflammation; stroke