Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain Journal Article
| Authors: | Panagiotakos, G.; Al Shamy, G.; Chan, B.; Abrams, R.; Greenberg, E.; Saxena, A.; Bradbury, M.; Edgar, M.; Gutin, P.; Tabar, V. |
| Article Title: | Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain |
| 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 fat 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 demonstrate 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 radiatidn, 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 oligodendrotype 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. © 2007 Panagiotakos et al. |
| Keywords: | controlled study; human tissue; nonhuman; radiation dose; brain radiation; nuclear magnetic resonance imaging; methodology; magnetic resonance imaging; animal; metabolism; animals; animal tissue; cell compartmentalization; cell division; radiotherapy; brain cortex; brain injury; neural stem cell; subventricular zone; pathology; radiation injury; necrosis; histology; radiation exposure; physiology; stem cell; brain; brain ventricle; quantitative analysis; interneuron; nerve fiber; interneurons; rat; cell subpopulation; stem cells; cell count; rats; rodentia; rats, sprague-dawley; cerebral cortex; brain region; x irradiation; sprague dawley rat; white matter; neuropathology; calretinin; olfactory bulb; corpus callosum; nerve cell necrosis; cerebral ventricles; oligodendroglia; demyelination; calcium-binding protein, vitamin d-dependent; myelin sheath; cell kinetics; calbindin; brain capillary; nerve cell growth |
| Journal Title: | PLoS ONE |
| Volume: | 2 |
| Issue: | 7 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2007-07-11 |
| Start Page: | e588 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0000588 |
| PUBMED: | 17622341 |
| PROVIDER: | scopus |
| PMCID: | PMC1913551 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 17 November 2011" - "Source: Scopus" |
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