title: Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia.
abstract: Ischemic stroke is caused by the interruption of cerebral blood flow that leads to brain damage with long-term sensorimotor deficits. Stem cell transplantation may recover functional deficit by replacing damaged brain. In this study, we attempted to test whether the human neural stem cells (NSCs) can improve the outcome in the rat brain with intravenous injection and also determine the migration, differentiation and the long-term viabilities of human NSCs in the rat brain. Focal cerebral ischemia was induced by intraluminal thread occlusion of middle cerebral artery (MCA). One day after surgery, the rats were randomly divided into two groups: NSCs-ischemia vs. Ischemia-only. Human NSCs infected with retroviral vector encoding beta galactosidase were intravenously injected in NSCs-ischemia group (5 x 10(6) cells) and the same amount of saline was injected in Ischemia-only group for control. The animals were evaluated for 4 weeks using turning in an alley (TIA) test, modified limb placing test (MLPT) and rotarod test. Transplanted cells were detected by X gal cytohistochemistry or beta gal immunohistochemistry with double labeling of other cell markers. The NSCs-ischemia group showed better performance on TIA test at 2 weeks, and MLPT and rotarod test from 3 weeks after ischemia compared with the Ischemia-only group. Human NSCs were detected in the lesion side and labeled with marker for neurons or astrocytes. Postischemic hemispheric atrophy was noted but reduced in NSCs-ischemia group. X gal+ cells were detected in the rat brain as long as 540 days after transplantation. Our data suggest intravenously transplanted human NSCs can migrate and differentiate in the rat brain with focal ischemia and improve functional recovery.
authors.affiliation: Department of Neurology, Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Seoul National University Hospital, Seoul National University, 28, Yongon-Dong, Chongro-Gu, Seoul 110-744, South Korea.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Kyung-Il
authors.initials: KI
authors.lastname: Park
authors.forename: Sang-Wuk
authors.initials: SW
authors.lastname: Jeong
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Park
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Lami
authors.initials: L
authors.lastname: Kang
authors.forename: Kyungmi
authors.initials: K
authors.lastname: Lee
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000209:etiology* / Q000378:metabolism / Q000601:surgery; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D007839:Functional Laterality / Q000502:physiology; D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000601:surgery; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000637:transplantation* / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D045442:Rotarod Performance Test / Q000379:methods; D012678:Sensation Disorders / Q000209:etiology / Q000601:surgery / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D014746:Vimentin; D010751:Phosphopyruvate Hydratase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside