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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain Ischemia / drug therapy*
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Brain Ischemia / metabolism
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Brain Ischemia / physiopathology
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Cell Division / drug effects
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Cell Division / physiology
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Cell Movement / drug effects
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Cell Movement / physiology
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Dendrites / drug effects
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Dendrites / metabolism
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Dendrites / ultrastructure
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Growth Substances / pharmacology*
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Growth Substances / therapeutic use
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Hippocampus / drug effects
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Hippocampus / growth & development*
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Hippocampus / ultrastructure
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Male
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Microscopy, Electron
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Microtubule-Associated Proteins / metabolism
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Nerve Degeneration / drug therapy
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Nerve Regeneration / drug effects
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Nerve Regeneration / physiology*
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Neural Pathways / drug effects
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Neural Pathways / growth & development
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Neural Pathways / ultrastructure
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Organ Culture Techniques
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism*
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Pyramidal Cells / ultrastructure
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Rats
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Rats, Wistar
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Recovery of Function / drug effects
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Recovery of Function / physiology
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Stem Cells / ultrastructure
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Synapses / drug effects
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Synapses / metabolism
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Synapses / ultrastructure
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Growth Substances
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Microtubule-Associated Proteins
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Transcription Factors