title: Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack.
abstract: SEE SUN ET AL DOI101093/AWW306 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: About 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack. As endothelial activation is a hallmark of cerebrovascular events, we postulated that this may also be true for transient ischaemic attack, and that it would be clinically relevant to develop non-invasive in vivo imaging to detect this endothelial activation. Using transcriptional and immunohistological analyses for adhesion molecules in a mouse model, we identified brain endothelial P-selectin as a potential biomarker for transient ischaemic attack. We thus developed ultra-sensitive molecular magnetic resonance imaging using antibody-based microparticles of iron oxide targeting P-selectin. This highly sensitive imaging strategy unmasked activated endothelial cells after experimental transient ischaemic attack and allowed discriminating transient ischaemic attack from epilepsy and migraine, two important transient ischaemic attack mimics. We provide preclinical evidence that combining conventional magnetic resonance imaging with molecular magnetic resonance imaging targeting P-selectin might aid in the diagnosis of transient ischaemic attack.
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Quenault
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Martinez de Lizarrondo
authors.affiliation: 2 CHU de Caen, Laboratoire des Explorations Fonctionnelles du Système Nerveux, 14000 Caen, France.|3 Medical School, CHU de Caen, 14000 Caen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Etard
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Orset
authors.affiliation: 4 Centre Universitaire de Ressources Biologiques, Université Caen-Normandie, Caen, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Haelewyn
authors.affiliation: 5 Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Segal
authors.affiliation: 5 Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.|6 CHU Caen, Department of Clinical Research, CHU Caen Côte de Nacre, 14000 Caen, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France.|7 CHU Caen, Stroke Unit, Department of Neurology, CHU Caen Côte de Nacre, 14000 Caen, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Touzé
authors.affiliation: 1 Normandie Univ, UNICAEN, INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Cyceron, 14000 Caen, France ali@cyceron.fr.
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D019007:P-Selectin / Q000378:metabolism*; D020521:Stroke / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019007:P-Selectin
keywords: P-selectin; cerebrovascular inflammation; mimics; molecular imaging; transient ischaemic attack