title: Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain.
abstract: Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia.
authors: Department of Anesthesiology, Kurume University School of Medicine, Fukuoka, Japan.
authors: Yuki
authors: Y
authors: Gotanda
authors: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Fan-Yan
authors: FY
authors: Wei
authors: Department of Anesthesiology, Kurume University School of Medicine, Fukuoka, Japan.
authors: Hideki
authors: H
authors: Harada
authors: Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan.
authors: Keisuke
authors: K
authors: Ohta
authors: Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan.
authors: Kei-Ichiro
authors: KI
authors: Nakamura
authors: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: tomikt@kumamoto-u.ac.jp.
authors: Kazuhito
authors: K
authors: Tomizawa
authors: Department of Anesthesiology, Kurume University School of Medicine, Fukuoka, Japan.
authors: Kazuo
authors: K
authors: Ushijima
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D021381:Protein Transport; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010455:Peptides; C015462:polyarginine
keywords: Protein transduction; brain; ischemia; poly-arginine