title: Serial MRI study of the enhanced therapeutic effects of liposome-encapsulated citicoline in cerebral ischemia.
abstract: Liposome encapsulation of active principles enhances their bioavailability to the brain. We investigated whether encapsulation of citicoline in liposomes increases its therapeutic effects in ischemia, performing a longitudinal MRI study of lesion volumes and edema in an animal model of stroke. Nineteen rats were submitted to permanent occlusion of the middle cerebral artery and treated with: (1) saline, (2) intraperitoneal citicoline (500mg/kg), (3) intravenous citicoline (48mg/kg), and (4) intravenous liposome-encapsulated citicoline (48mg/kg). Lesion volumes were measured by MRI at days 0, 1, 3 and 7 following surgery. Encapsulation in liposomes increased the therapeutic effects of citicoline, as reflected by a 32% reduction of the infarct sizes at day 7, in contrast with controls where infarct sizes at day 7 increased by 39%, respect to values at day 0. Intravenously injected citicoline reduced infarct sizes by 9% while intraperitoneal citicoline resulted in an increase of infarct sizes by 10%. A slight (not significant) reduction of edema formation was observed for animals treated with citicoline, in all of its delivery forms. Liposome-encapsulated citicoline causes a noticeable reduction in lesion volumes as compared to free citicoline (either i.p. or i.v.) at days 1, 3 and 7 following permanent stroke.
authors.affiliation: Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario de Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain. pedro.ramos@usc.es,
authors.forename: Pedro
authors.initials: P
authors.lastname: Ramos-Cabrer
authors.forename: Jesús
authors.initials: J
authors.lastname: Agulla
authors.forename: Bárbara
authors.initials: B
authors.lastname: Argibay
authors.forename: María
authors.initials: M
authors.lastname: Pérez-Mato
authors.forename: José
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000662:veterinary; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D008081:Liposomes; D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline