title: Implications of irradiating the subventricular zone stem cell niche.
abstract: Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs) reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Stem Cells, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville 41092, Spain.
authors.forename: Vivian
authors.initials: V
authors.lastname: Capilla-Gonzalez
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Bonsu
authors.affiliation: Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Redmond
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, University of Valencia, CIBERNED, Paterna 46980, Valencia, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: aquinon2@jhmi.edu.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
mesh_terms: D000818:Animals; D001921:Brain / Q000528:radiation effects; D063646:Carcinogenesis; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055153:Stem Cell Niche
keywords: Brain tumor; Neural stem cells; Neurogenesis; Radiation; Subventricular zone