Published Online
on April 8, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on October 8, 2003
Revised on December 29, 2003
Accepted on February 2, 2004

Neurogenesis After Transient Global Ischemia in the Adult Hippocampus Visualized by Improved Retroviral Vector

Ryota Tanaka MD, PhD; Kazuo Yamashiro MD; Hideki Mochizuki MD; Nei Cho MD; Masafumi Onodera MD; Yoshikuni Mizuno MD; and Takao Urabe MD, PhD^*

From the Department of Neurology (R.T., K.Y., H.M., N.C., Y.M., T.U.), Research Institute of Old Ages (H.M., Y.M.), Juntendo University School of Medicine, Tokyo; Department of Hematology (M.O.), Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

^* To whom correspondence should be addressed. E-mail: t_urabe{at}med.juntendo.ac.jp.

Background and Purpose--Neurogenesis has been observed in the dentate gyrus of the adult hippocampus; however, the mechanisms involved in this process are still only partly understood. In this study, we visualized the proliferation, migration, and differentiation of neuronal progenitor cells in the dentate gyrus induced by ischemic stress using improved retroviral vector.

Methods--Improved retroviral vector expressing enhanced green fluorescent protein (EGFP) as a transgene was injected into the dentate gyrus of adult Mongolian gerbils. After 48 hours, transient global ischemia (TGI) was induced by bilateral common carotid artery occlusion for 5 minutes using aneurysm clips. The morphological and immunohistological features of newly-generated cells in the dentate gyrus were analyzed at various times thereafter.

Results--At 48 hours after viral injection, almost all EGFP-positive dividing cells were found in the subgranule layer (SGL). These cells proliferated and migrated to the granule cell layer (GCL), expressing the developing neuronal markers polysialic acid and doublecortin, and differentiated to neuronal nuclei-positive or calbindin-positive mature granule cells at 30 days after TGI or sham-operation. The number of GFP-positive cells in the GCL was significantly higher (P<0.05) in the ischemic animals at 30 days than in sham-operated gerbils.

Conclusions--We saw neurogenesis in the adult dentate gyrus. Furthermore, we showed that ischemic stress promoted the proliferation and normal development of neurons at this site.

Key words: progenitor cell • cerebral ischemia, transient • gerbils • hippocampus

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