title: Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats.
abstract: BACKGROUND
  Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats.
  
  
  METHODS
  This was an experimental study.
  
  
  METHODS
  A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test.
  
  
  RESULTS
  Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group.
  
  
  CONCLUSIONS
  A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans.
  
  
  CONCLUSIONS
  The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model.
authors.affiliation: Y. Sasaki, PT, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan, and Department of Rehabilitation, Sapporo Medical University School of Medicine.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: M. Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut. msasaki@sapmed.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Y. Kataoka-Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kataoka-Sasaki
authors.affiliation: M. Nakazaki, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Masahito
authors.initials: M
authors.lastname: Nakazaki
authors.affiliation: H. Nagahama, RT, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagahama
authors.affiliation: J. Suzuki, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Junpei
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: D. Tateyama, BS, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tateyama
authors.affiliation: S. Oka, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: T. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Namioka
authors.affiliation: A. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Ai
authors.initials: A
authors.lastname: Namioka
authors.affiliation: R. Onodera, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
authors.forename: Rie
authors.initials: R
authors.lastname: Onodera
authors.affiliation: T. Mikami, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mikami
authors.affiliation: M. Wanibuchi, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Wanibuchi
authors.affiliation: M. Kakizawa, PT, Department of Rehabilitation, Sapporo Medical University School of Medicine.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kakizawa
authors.affiliation: S. Ishiai, MD, PhD, Department of Rehabilitation, Sapporo Medical University School of Medicine.
authors.forename: Sumio
authors.initials: S
authors.lastname: Ishiai
authors.affiliation: J.D. Kocsis, PhD, Department of Neurology, Yale University School of Medicine, and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Kocsis
authors.affiliation: O. Honmou, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine; Department of Neurology, Yale University School of Medicine; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071939:Stroke Rehabilitation / Q000379:methods*