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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Active Transport

Cell Nucleus

Animals

Apoptosis

Body Weight

Brain/*embryology

Caspases/*antagonists & inhibitors/metabolism

Cell Death

Cell Proliferation

DNA Fragmentation

Dose-Response Relationship

Radiation

Enzyme Activation

Enzyme Inhibitors/*pharmacology

Erythropoietin/metabolism/*pharmacology

Hippocampus/metabolism

Immunohistochemistry

In Situ Nick-End Labeling

Ki-67 Antigen/biosynthesis

Mice

Mice

Inbred C57BL

Myelin Basic Proteins/metabolism

Proteins/metabolism

Rats

Rats

Wistar

Research Support

Non-U.S. Gov't

Stem Cells/*pathology

Time Factors

Tumor Suppressor Protein p53/metabolism

X-Linked Inhibitor of Apoptosis Protein

irradiation

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)