Isolation and characterization of neural stem/progenitor cells from post-stroke cerebral cortex in mice.
The CNS has the potential to marshal strong reparative mechanisms, including activation of endogenous neurogenesis, after a brain injury such as stroke. However, the response of neural stem/progenitor cells to stroke is poorly understood. Recently, neural stem/progenitor cells have been identified in the cerebral cortex, as well as previously recognized regions such as the subventricular or subgranular zones of the hippocampus, suggesting that a contribution of cortex-derived neural stem/progenitor cells may repair ischemic lesions of the cerebral cortex. In the present study, using a highly reproducible murine model of cortical infarction, we have found nestin-positive cells in the post-stroke cerebral cortex, but not in the non-ischemic cortex. Cells obtained from the ischemic core of the post-stroke cerebral cortex formed neurosphere-like cell clusters expressing nestin; such cells had the capacity for self-renewal and differentiated into electrophysiologically functional neurons, astrocytes and myelin-producing oligodendrocytes. Nestin-positive cells from the stroke-affected cortex migrated into the peri-infarct area and differentiated into glial cells in vivo. Although we could not detect differentiation of nestin-positive cells into neurons in vivo, our current observations indicate that endogenous neural stem/progenitors with the potential to become neurons can develop within post-stroke cerebral cortex.
Nakagomi
Takayuki
T
Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan. nakagomi@hyo-med.ac.jp
Taguchi
Akihiko
A
Fujimori
Yoshihiro
Y
Saino
Orie
O
Nakano-Doi
Akiko
A
Kubo
Shuji
S
Gotoh
Akinobu
A
Soma
Toshihiro
T
Yoshikawa
Hiroo
H
Nishizaki
Tomoyuki
T
Nakagomi
Nami
N
Stern
David M
DM
Matsuyama
Tomohiro
T
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000503:physiopathology*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin