title: Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.
abstract: The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France; Department of Neurology, University Hospital, Dijon, F-21000, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Rodier
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France; Département Génie Biologique, IUT, Dijon, F-21078, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Quirié
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Prigent-Tessier
authors.affiliation: Department of Neurology, University Hospital, Dijon, F-21000, France; Centre d'Epidémiologie des Populations, EA4184, Dijon, F-21000, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Béjot
authors.affiliation: Department of Neurology, University Hospital, Dijon, F-21000, France; Centre d'Epidémiologie des Populations, EA4184, Dijon, F-21000, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Jacquin
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Mossiat
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Marie
authors.affiliation: Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, F-21078, France; Université de Bourgogne Franche-Comté, Dijon, F-21079, France; Département Génie Biologique, IUT, Dijon, F-21078, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Garnier
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011379:Prognosis; D051381:Rats; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D005343:Fibrinolytic Agents; C579455:BDNF protein, human; D010959:Tissue Plasminogen Activator