title: Greatly improved neuroprotective efficiency of citicoline by stereotactic delivery in treatment of ischemic injury.
abstract: Limited penetration of neuroprotective drug citicoline into the central nervous system (CNS) by systemic administration led to poor efficiency. A novel method of stereotactic drug delivery was explored to make citicoline bypass the blood brain barrier (BBB) and take effect by direct contact with ischemic neurons. A permanent middle cerebral artery occlusion (pMCAO) model of rats was prepared. To get the optimal conditions for citicoline administration by the novel stereotactic delivery pathway, magnetic resonance imaging (MRI) tracer method was used, and a dose-dependent effect was given. Examinations of MRI, behavior evaluation, infarct volume assessment and histological staining were performed to evaluate the outcome. This MRI-guided stereotactic delivery of citicoline resulted in a notable reduction (>80%) in infarct size and a delayed ischemic injury in cortex 12 hours after onset of acute ischemia when compared with the systematic delivery. The improved neuroprotective efficiency was realized by a full distribution of citicoline in most of middle cerebral artery (MCA) territory and an adequate drug reaction in the involved areas of the brain. Brain lesions of treated rats by stereotactic delivery of citicoline were well predicted in the lateral ventricle and thalamus due to a limited drug deposition by MRI tracer method. Our study realized an improved neuroprotective efficiency of citicoline by stereotactic delivery, and an optimal therapeutic effect of this administration pathway can be achieved under MRI guidance.
authors.affiliation: Department of Radiology, Peking University Third Hospital, North Huayuan Road No. 49, Haidian District, Beijing 100191, China.
authors.forename: Fangjingwei
authors.initials: F
authors.lastname: Xu
authors.lastname: Hongbin Han
authors.forename: Junhao
authors.initials: J
authors.lastname: Yan
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: He
authors.forename: Weiguo
authors.initials: W
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Fugen
authors.initials: F
authors.lastname: Zhou
authors.forename: Kejia
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D014018:Tissue Distribution
chemical_list: D018696:Neuroprotective Agents; D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline