title: Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury.
abstract: Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24h after TBI, MSCs (1×10(6)cells/100μl) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, Japan; Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Toyoshima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kameda
authors.forename: Tomohito
authors.initials: T
authors.lastname: Hishikawa
authors.forename: Koji
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiu
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Haruma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005990:Glycerol / Q000627:therapeutic use; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D045164:Mesenchymal Stem Cell Transplantation; D009043:Motor Activity / Q000187:drug effects; D010539:Permeability; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D008353:Mannitol; D005990:Glycerol
keywords: Hypertonic solution; Mesenchymal stem cells; Traumatic brain injury