title: Enhanced brain-derived neurotrophic factor delivery by ultrasound and microbubbles promotes white matter repair after stroke.
abstract: Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke. This technique was shown to be safe, given there were no cases of hemorrhagic transformation or blood brain barrier (BBB) leakage. UTMD treatment was associated with increased brain BDNF levels at 4 h after administration. Targeted ultrasound delivery of BDNF improved functional recovery associated with fiber tract connectivity restoration, increasing oligodendrocyte markers and remyelination compared to BDNF alone administration in an experimental animal model of white matter injury.
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Rodríguez-Frutos
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Otero-Ortega
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ramos-Cejudo
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martínez-Sánchez
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Barahona-Sanz
authors.affiliation: Laboratory for Imaging and Spectroscopy by Magnetic Resonance LISMAR, Institute of Biomedical Research Alberto Sols, CSIC-UAM, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Navarro-Hernanz
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Gómez-de Frutos
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain. Electronic address: exuperio.diez@salud.madrid.org.
authors.forename: Exuperio
authors.initials: E
authors.lastname: Díez-Tejedor
authors.affiliation: Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Madrid, Spain. Electronic address: mgutierrezfernandez@salud.madrid.org.
authors.forename: María
authors.initials: M
authors.lastname: Gutiérrez-Fernández
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D045423:Microbubbles; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D000069453:Ultrasonic Waves; D014465:Ultrasonics / Q000379:methods*; D066127:White Matter / Q000187:drug effects* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; Brain repair; Microbubbles; Subcortical stroke; Ultrasound; White matter injury