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(Stroke. 2001;32:1890.)
© 2001 American Heart Association, Inc.

Original Contributions

Neurogenesis by Progenitor Cells in the Ischemic Adult Rat Hippocampus

Yoshiki Yagita, MD, PhD; Kazuo Kitagawa, MD, PhD; Toshiho Ohtsuki, MD, PhD; Ken-ichiro Takasawa, MD; Takaki Miyata, PhD; Hideyuki Okano, MD, PhD; Masatsugu Hori, MD, PhD Masayasu Matsumoto, MD, PhD

From the Division of Strokology, Department of Internal Medicine and Therapeutics (Y.Y., K.K., T.O., K-i.T., M.M.), Department of Neuroanatomy, Biomedical Research Center (T.M., H.O.), and Department of Clinical Neuroscience (M.M.), Osaka University Graduate School of Medicine, Osaka, Japan.

Correspondence to Dr Kazuo Kitagawa, Division of Strokology, Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan. E-mail kitagawa{at}medone.med.osaka-u.ac.jp

Background and Purpose—— Recently, there has been great interest in adult neurogenesis. We investigated whether transient forebrain ischemia could influence the proliferation of neuronal progenitor in the subgranular zone (SGZ) of the rat hippocampus and whether aging could influence the neurogenesis after ischemia.

Methods—— Male Wistar rats were subjected to 4-vessel occlusion model. We used a bromodeoxyuridine (BrdU) labeling method to identify the postproliferation cells and double-immunostaining with confocal microscopy to determine the cell phenotype.

Results—— The number of BrdU-positive cells in the SGZ increased 5.7-fold 8 days after ischemia, compared with the control. BrdU-positive cells formed clusters, which suggested that these cells had divided from an original progenitor cell, and expressed Musashi1 (Msi1), a marker of neural stem/progenitor cells. Although astrocytes also expressed Msi1 in the adult brain, Msi1-positive cells that formed clusters in the SGZ did not express glial fibrillary acidic protein, an astrocyte marker. About 70% of all BrdU-positive cells in the SGZ represented the neuronal phenotype 4 weeks after the BrdU injection. Although proliferation of progenitor cells was stimulated in both young and older animals, aging accelerated the reduction in newborn cells after ischemia.

Conclusions—— Our results indicate that ischemic stress stimulated the proliferation of neuronal progenitor cells in the SGZ of both young and old rats but resulted in increased neurogenesis only in young animals. Our findings will be important in developing therapeutic intervention to enhance endogenous neurogenesis after brain injury.

Key Words: aging • cerebral ischemia, global • cerebral ischemia, transient • hippocampus • neurogenesis • rats

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