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(Stroke. 2009;40:e606.)
© 2009 American Heart Association, Inc.

Original Contributions

Induced Spreading Depression Evokes Cell Division of Astrocytes in the Subpial Zone, Generating Neural Precursor-Like Cells and New Immature Neurons in the Adult Cerebral Cortex

Jing-Hui Xue, MD, PhD; Hiroji Yanamoto, MD, DMSc; Yukako Nakajo, MSc; Norimitsu Tohnai, PhD; Yoshikazu Nakano, BSc; Takuya Hori, MCE; Koji Iihara, MD, PhD Susumu Miyamoto, MD, PhD

From the Lab for Cerebrovascular Disorders (J.-H.X., H.Y., Y. Nakajo, N.T., Y. Nakano, T.H.), Research Institute of National Cardio-Vascular Center (NCVC), Suita, Osaka, Japan; the Department of Cerebrovascular Surgery (H.Y., K.I., S.M.), NCVC, Suita, Osaka, Japan; the Research Laboratory (Y. Nakano), Rakuwakai Otowa Hospital, Kyoto, Japan; the Department of Neurosurgery (J.-H.X.), First Affiliated Hospital, General Hospitals of PLA, Beijing, PR China; Hakuju (T.H.), Institute for Health Science, Tokyo, Japan; the Department of Cardiovascular Science (H.Y., Y. Nakajo), Osaka University Graduate School of Medicine, Suita, Osaka, Japan; and the Department of Materials and Life Science (N.T.), Osaka University Graduate School of Engineering, Suita, Osaka, Japan.

Correspondence to Hiroji Yanamoto, MD, DMSc, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Japan 565-8565. E-mail hyanamot{at}res.ncnv.go.jp

Background and Purpose— New immature neurons appear out of the germinative zone, in cortical Layers V to VI, after induced spreading depression in the adult rat brain. Because neural progenitors have been isolated in the cortex, we set out to determine whether a subgroup of mature cells in the adult cortex has the potential to divide and generate neural precursors.

Methods— We examined the expression of endogenous markers of mitotic activity, proliferating cell nuclear antigen, and vimentin as a marker for neuronal progenitor cells, if any, in the adult rat cortex after spreading depression stimulation. Immunohistochemical analysis was also performed using antibodies for proliferating cell nuclear antigen, for vimentin, and for nestin. Nestin is a marker for activity dividing neural precursors.

Results— At the end of spreading depression (Day 0), glial fibrillary acidic protein-positive cells in the subpial zone and cortical Layer I demonstrated increased mitotic activity, expressing vimentin and nestin. On Day 1, nestin⁺ cells were found spreading in deeper cortical layers. On Day 3, vimentin^–/nestin⁺, neural precursor-like cells appeared in cortical Layers V to VI. On Day 6, new immature neurons appeared in cortical Layers V to VI. Induced spreading depression evokes cell division of astrocytes residing in the subpial zone, generating neural precursor-like cells.

Conclusions— Although neural precursor-like cells found in cortical Layers V to VI might have been transferred from the germinative zone rather than the cortical subpial zone, astrocytic cells in the subpial zone may be potent neural progenitors that can help to reconstruct impaired central nervous system tissue. Special caution is required when observing or treating spreading depression waves accompanying pathological conditions in the brain.

Key Words: astrocytes • ischemia • neural stem cells • neurophysiology • neuroregeneration • stroke management • stroke recovery