Bone marrow stromal cell transplantation attenuates cognitive dysfunction due to chronic cerebral ischemia in rats.
OBJECTIVE
This study was aimed to elucidate if bone marrow stromal cells (BMSC) could ameliorate cognitive dysfunction due to chronic cerebral ischemia when transplanted into the brain.


METHODS
The BMSC were harvested from green fluorescence protein (GFP)-expressing mice. Wistar rats were subjected to bilateral common carotid artery (CCA) ligation. The BMSC (4 × 10⁵ cells) or vehicle were stereotactically injected into the right striatum 24 h after the insult. Cognitive function was evaluated with the Morris water maze task after 3 and 5 weeks. Histological analysis was performed after 6 weeks.


RESULTS
Cognitive function was significantly impaired in the vehicle-transplanted animals, when compared with the non-CCA-ligation animals. BMSC transplantation significantly improved it. The BMSC were widely distributed in the ischemic brain, including the neocortex, white matter and hippocampus, and some of them expressed the phenotypes of neurons, astrocytes and endothelium. They also significantly ameliorated white matter damage.


CONCLUSIONS
These findings strongly suggest that the BMSC may have the potential to attenuate white matter injury and improve cognitive dysfunction due to chronic cerebral ischemia. The present results would shed light on the potential of a novel strategy, cell therapy against ischemia-related cognitive dysfunction.
Shichinohe
Hideo
H
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Sugiyama
Taku
T
Ito
Masaki
M
Kawabori
Masahito
M
D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D017536:Carotid Artery, Common; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000473:pathology / Q000601:surgery; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation
D049408:Luminescent Agents; D049452:Green Fluorescent Proteins