Altered brain morphology after focal radiation reveals impact of off-target effects: Implications for white matter development and neurogenesis

Kiran G. Beera, Yu Qing Li, Jun Dazai, James Stewart, Shannon Egan, Mashal Ahmed, C. Shun Wong, David A. Jaffray, Brian J. Nieman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Background Children with brain tumors treated with cranial radiation therapy (RT) often exhibit cognitive late effects, commonly associated with reduced white matter (WM) volume and decreased neurogenesis. The impact of radiation damage in particular regions or tissues on brain development as a whole has not been elucidated. Methods We delivered whole-brain or focal radiation (8 Gy single dose) to infant mice. Focal treatments targeted white matter (anterior commissure), neuronal (olfactory bulbs), or neurogenic (subventricular zone) regions. High-resolution ex vivo MRI was used to assess radiation-induced volume differences. Immunohistochemistry for myelin basic protein and doublecortin was performed to assess associated cellular changes within white matter and related to neurogenesis, respectively. Results Both whole-brain and focal RT in infancy resulted in volume deficits in young adulthood, with whole-brain RT resulting in the largest deficits. RT of the anterior commissure, surprisingly, showed no impact on its volume or on brain development as a whole. In contrast, RT of the olfactory bulbs resulted in off-target volume reduction in the anterior commissure and decreased subventricular zone neurogenesis. RT of the subventricular zone likewise produced volume deficits in both the olfactory bulbs and the anterior commissure. Similar off-target effects were found in the corpus callosum and parietal cortex. Conclusions Our results demonstrate that radiation damage locally can have important off-target consequences for brain development. These data suggest that WM may be less radiosensitive than volume change alone would indicate and have implications for region-sparing radiation treatments aimed at reducing cognitive late effects.

Original languageEnglish (US)
Pages (from-to)788-798
Number of pages11
JournalNeuro-oncology
Volume20
Issue number6
DOIs
StatePublished - May 18 2018
Externally publishedYes

Keywords

  • MRI
  • brain development
  • neurogenesis
  • radiation
  • white matter

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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