title: Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats.
abstract: This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan; skuroda@med.u-toyama.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shichinohe
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Hisayasu
authors.initials: H
authors.lastname: Saito
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010042:Ouabain / Q000633:toxicity; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D059409:Stroke, Lacunar / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery*; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D010042:Ouabain