Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

H Fukuda; A Fukuda; C Zhu; L Korhonen; J Swanpalmer; S Hertzman; M Leist; B Lannering; D Lindholm; T Björk-Eriksson; I Marky; K Blomgren

doi:10.1038/sj.cdd.4401472

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

Cell Death Differ. 2004 Nov;11(11):1166-78. doi: 10.1038/sj.cdd.4401472.

Authors

H Fukuda¹, A Fukuda, C Zhu, L Korhonen, J Swanpalmer, S Hertzman, M Leist, B Lannering, D Lindholm, T Björk-Eriksson, I Marky, K Blomgren

Affiliation

¹ Perinatal Center, Department of Physiology, Göteborg University, Box 432, SE 405 30 Göteborg, Sweden.

PMID: 15243583
DOI: 10.1038/sj.cdd.4401472

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

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Animals
Apoptosis
Body Weight
Brain / embryology*
Caspase 3
Caspase 9
Caspase Inhibitors*
Caspases / metabolism
Cell Death
Cell Proliferation
DNA Fragmentation
Dose-Response Relationship, Radiation
Enzyme Activation
Enzyme Inhibitors / pharmacology*
Erythropoietin / metabolism
Erythropoietin / pharmacology*
Hippocampus / metabolism
Immunohistochemistry
In Situ Nick-End Labeling
Ki-67 Antigen / biosynthesis
Mice
Mice, Inbred C57BL
Myelin Basic Protein / metabolism
Proteins / metabolism
Rats
Rats, Wistar
Stem Cells / pathology*
Time Factors
Tumor Suppressor Protein p53 / metabolism
X-Linked Inhibitor of Apoptosis Protein

Substances

Caspase Inhibitors
Enzyme Inhibitors
Ki-67 Antigen
Myelin Basic Protein
Proteins
Tumor Suppressor Protein p53
X-Linked Inhibitor of Apoptosis Protein
Erythropoietin
Casp3 protein, mouse
Casp3 protein, rat
Casp9 protein, mouse
Casp9 protein, rat
Caspase 3
Caspase 9
Caspases