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PLoS One ; 2(7): e588, 2007 Jul 11.
Article in English | MEDLINE | ID: mdl-17622341

ABSTRACT

BACKGROUND: The cellular basis of long term radiation damage in the brain is not fully understood. METHODS AND FINDINGS: We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries. CONCLUSIONS: This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.


Subject(s)
Brain/radiation effects , Oligodendroglia/radiation effects , Stem Cells/radiation effects , Animals , Calbindin 2 , Cell Division/radiation effects , Cerebral Cortex/radiation effects , Cerebral Ventricles/physiology , Cerebral Ventricles/radiation effects , Corpus Callosum/anatomy & histology , Corpus Callosum/radiation effects , Female , Humans , Interneurons/physiology , Interneurons/radiation effects , Magnetic Resonance Imaging , Myelin Sheath/pathology , Myelin Sheath/radiation effects , Necrosis , Olfactory Bulb/pathology , Olfactory Bulb/radiation effects , Radiotherapy/adverse effects , Radiotherapy/methods , Rats , Rats, Sprague-Dawley , S100 Calcium Binding Protein G/metabolism , S100 Calcium Binding Protein G/radiation effects
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