Abstract
One hemisphere of postnatal day 8 (P8) rats or P10 mice was irradiated with a single dose of 4-12 Gy, and animals were killed from 2 h to 8 weeks after irradiation (IR). In the subventricular zone (SVZ) and the granular cell layer (GCL) of the dentate gyrus, harboring neural and other progenitor cells, nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active caspase-3, apoptosis-inducing factor and TUNEL (6-24 h). Ki67-positive (proliferating) cells had disappeared by 12 h and partly reappeared by 7 days post-IR. The SVZ and GCL areas decreased approximately 50% 7 days after IR. The development of white matter was hampered, resulting in 50-70% less myelin basic protein staining. Pretreatment with erythropoietin did not confer protection against IR. Caspase inhibition by overexpression of XIAP prevented caspase-9 and caspase-3 activation but not cell death, presumably because of increased caspase-independent cell death.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Apoptosis
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Body Weight
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Brain / embryology*
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Caspase 3
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Caspase 9
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Caspase Inhibitors*
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Caspases / metabolism
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Cell Death
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Cell Proliferation
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DNA Fragmentation
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Dose-Response Relationship, Radiation
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Enzyme Activation
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Enzyme Inhibitors / pharmacology*
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Erythropoietin / metabolism
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Erythropoietin / pharmacology*
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Hippocampus / metabolism
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Immunohistochemistry
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In Situ Nick-End Labeling
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Ki-67 Antigen / biosynthesis
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Mice
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Mice, Inbred C57BL
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Myelin Basic Protein / metabolism
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Proteins / metabolism
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Rats
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Rats, Wistar
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Stem Cells / pathology*
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Time Factors
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Tumor Suppressor Protein p53 / metabolism
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X-Linked Inhibitor of Apoptosis Protein
Substances
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Caspase Inhibitors
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Enzyme Inhibitors
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Ki-67 Antigen
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Myelin Basic Protein
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Proteins
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Tumor Suppressor Protein p53
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X-Linked Inhibitor of Apoptosis Protein
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Erythropoietin
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Casp3 protein, mouse
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Casp3 protein, rat
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Casp9 protein, mouse
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Casp9 protein, rat
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Caspase 3
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Caspase 9
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Caspases