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Irradiation to the young mouse brain caused long-term,progressive depletion of neurogenesis but did not disrupt the neurovascular niche
Authors:Martina Bostr?m  Marie Kalm  Niklas Karlsson  Nina Hellstr?m Erkenstam  Klas Blomgren
Affiliation:1.Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;2.Department of Women''s and Children''s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;3.Department of Pediatrics, University of Gothenburg, Queen Silvia Children''s Hospital, Gothenburg, Sweden
Abstract:We investigated the effects of ionizing radiation on microvessel structure and complexity in the hippocampus. We also assessed neurogenesis and the neurovascular niche. Postnatal day 14 male C57BL/6 mice received a single dose of 8 Gy to the whole brain and were killed 6 hours, 1 week, 7 weeks, or 1 year later. Irradiation decreased the total number of microvessels and branching points from 1 week onwards and decreased the total microvessel area 1 and 7 weeks after irradiation. After an initial increase in vascular parameter densities, concomitant with reduced growth of the hippocampus, the densities normalized with time, presumably adapting to the needs of the surrounding nonvascular tissue. Irradiation decreased the number of neural stem and progenitor cells in the hippocampus. The relative loss increased with time, resulting in almost completely ablated neurogenesis (DCX+ cells) 1 year after irradiation (77% decreased 1 week, 86% decreased 7 weeks, and 98% decreased 1 year after irradiation compared with controls). After irradiation, the distance between undifferentiated stem cells and microvessels was unaffected, and very few dying endothelial cells were detected. Taken together, these results indicate that the vasculature adjusts to the surrounding neural and glial tissue after irradiation, not vice-versa.
Keywords:angiogenesis   endothelium   hippocampus   neural stem cells   radiotherapy
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