Neurogenesis by progenitor cells in the ischemic adult rat hippocampus

Yoshiki Yagita, Kazuo Kitagawa, Toshiho Ohtsuki, Ken Ichiro Takasawa, Takaki Miyata, Hideyuki Okano, Masatsugu Hori, Masayasu Matsumoto

Research output: Contribution to journalArticlepeer-review

141 Citations (Scopus)


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 Musashi I (Msi I), a marker of neural stem/progenitor cells. Although astrocytes also expressed Msi 1 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.

Original languageEnglish
Pages (from-to)1890-1896
Number of pages7
Issue number8
Publication statusPublished - 2001
Externally publishedYes


  • Aging
  • Cerebral ischemia, global
  • Cerebral ischemia, transient
  • Hippocampus
  • Neurogenesis
  • Rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing


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