Publication Type:Journal Article
Source:Cell Stem Cell, Volume 12, Issue 4, p.426-39 (2013)
Keywords:Animals, Astrocytes, Brain Injuries, Cell Death, Cell Proliferation, Cell Separation, Cerebral Cortex, Disease Models, Animal, Gliosis, Hedgehog Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Nerve Tissue Proteins, Neural Stem Cells, Neuroglia, Neurons, Signal Transduction, Spheroids, Cellular
As a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, we had demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In the present study, we demonstrate that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog (SHH) is the signal that acts directly on the astrocytes and is necessary and sufficient to elicit the stem cell response both in vitro and in vivo. These findings provide a molecular basis for how cells with neural stem cell lineage emerge at sites of brain injury and imply that the high levels of SHH known to enter the brain from extraneural sources after invasive injury can trigger this response.