Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors

Hirofumi Nakatomi, Toshihiko Kuriu, Shigeo Okabe, Shin ichi Yamamoto, Osamu Hatano, Nobutaka Kawahara, Akira Tamura, Takaaki Kirino, Masato Nakafuku

Research output: Contribution to journalArticlepeer-review

1291 Citations (Scopus)

Abstract

The adult brain is extremely vulnerable to various insults. The recent discovery of neural progenitors in adult mammals, however, raises the possibility of repairing damaged tissue by recruiting their latent regenerative potential. Here we show that activation of endogenous progenitors leads to massive regeneration of hippocampal pyramidal neurons after ischemic brain injury. Endogenous progenitors proliferate in response to ischemia and subsequently migrate into the hippocampus to regenerate new neurons. Intraventricular infusion of growth factors markedly augments these responses, thereby increasing the number of newborn neurons. Our studies suggest that regenerated neurons are integrated into the existing brain circuitry and contribute to ameliorating neurological deficits. These results expand the possibility of novel neuronal cell regeneration therapies for stroke and other neurological diseases.

Original languageEnglish
Pages (from-to)429-441
Number of pages13
JournalCell
Volume110
Issue number4
DOIs
Publication statusPublished - 2002 Aug 23
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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