title: Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.
abstract: Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.
authors.affiliation: Institute of Neurology (Edinger Institute), Frankfurt University Medical School Frankfurt, 60528 Frankfurt, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kraft
authors.affiliation: Focus Program Translational Neuroscience (FTN) and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany; Faculty of Psychology, Diego Portales University, Santiago, Chile.
authors.forename: Eduardo Rosales
authors.initials: ER
authors.lastname: Jubal
authors.affiliation: Institute of Neurology (Edinger Institute), Frankfurt University Medical School Frankfurt, 60528 Frankfurt, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: von Laer
authors.affiliation: Dr. Senckenberg Institute of Pathology, Frankfurt University Medical School, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 60528 Frankfurt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.affiliation: Cellular Neuroscience, Max Delbrück Centre for Molecular Medicine (MDC) in the Helmholtz Society, 13092 Berlin, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rocha
authors.affiliation: Institute of Neurology (Edinger Institute), Frankfurt University Medical School Frankfurt, 60528 Frankfurt, Germany.
authors.forename: Moyo
authors.initials: M
authors.lastname: Grebbin
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Cellular Neuroscience, Max Delbrück Centre for Molecular Medicine (MDC) in the Helmholtz Society, 13092 Berlin, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
authors.affiliation: Focus Program Translational Neuroscience (FTN) and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stroh
authors.affiliation: Institute of Neurology (Edinger Institute), Frankfurt University Medical School Frankfurt, 60528 Frankfurt, Germany. Electronic address: stefan.momma@kgu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Momma
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D002465:Cell Movement; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium
keywords: astrocytes; calcium signaling; neural stem cells; notch; stroke