Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors.
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.
Department of Neurobiology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Japan.
Hirofumi
H
Nakatomi
Toshihiko
T
Kuriu
Shigeo
S
Okabe
Shin-ichi
S
Yamamoto
Osamu
O
Hatano
Nobutaka
N
Kawahara
Akira
A
Tamura
Takaaki
T
Kirino
Masato
M
Nakafuku
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D006133:Growth Substances; D008869:Microtubule-Associated Proteins; D014157:Transcription Factors