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PMID: 12202033 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Cell ·Vol. 110 ·No. 4 ·2002-08-23 ·Pages 429-41

Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M

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.

MeSH Terms
Animals Brain Ischemia/drug therapy,metabolism,physiopathology Cell Division/drug effects,physiology Cell Movement/drug effects,physiology Dendrites/drug effects,metabolism,ultrastructure Excitatory Postsynaptic Potentials/drug effects,physiology Growth Substances/pharmacology,therapeutic use Hippocampus/drug effects,growth & development,ultrastructure Male Microscopy, Electron Microtubule-Associated Proteins/metabolism Nerve Degeneration/drug therapy,metabolism,physiopathology Nerve Regeneration/drug effects,physiology Neural Pathways/drug effects,growth & development,ultrastructure Neuronal Plasticity/drug effects,physiology Organ Culture Techniques Pyramidal Cells/drug effects,metabolism,ultrastructure Rats Rats, Wistar Recovery of Function/drug effects,physiology Stem Cells/drug effects,metabolism,ultrastructure Synapses/drug effects,metabolism,ultrastructure Transcription Factors/genetics,metabolism Up-Regulation/drug effects,physiology
Chemicals
Growth Substances Microtubule-Associated Proteins Transcription Factors
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Nakatomi Hirofumi
Department of Neurobiology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Japan.
Kuriu Toshihiko
Okabe Shigeo
Yamamoto Shin-ichi
Hatano Osamu
Kawahara Nobutaka
Tamura Akira
Kirino Takaaki
Nakafuku Masato
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
2002-08-23
Pages
429-41
Language
English
Region
United States
NLM ID
0413066
Subset
IM
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