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TitleReactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog. [corrected].
Publication TypeJournal Article
Year of Publication2013
AuthorsSirko, Swetlana, Gwendolyn Behrendt, Pia Annette Johansson, Pratibha Tripathi, Marcos Costa, Sarah Bek, Christophe Heinrich, Steffen Tiedt, Dilek Colak, Martin Dichgans, Isabel Rebekka Fischer, Nikolaus Plesnila, Matthias Staufenbiel, Christian Haass, Marina Snapyan, Armen Saghatelyan, Li-Huei Tsai, André Fischer, Kay Grobe, Leda Dimou, and Magdalena Götz
JournalCell Stem Cell
Volume12
Issue4
Pagination426-39
Date Published2013 Apr 4
ISSN1875-9777
KeywordsAnimals, 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
Abstract

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.

DOI10.1016/j.stem.2013.01.019
Alternate JournalCell Stem Cell
PubMed ID23561443
Grant ListR01 NS051874 / NS / NINDS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States