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Fractionation enhances acute oligodendrocyte progenitor cell radiation sensitivity and leads to long term depletion
Author(s) -
Begolly Sage,
Olschowka John A.,
Love Tanzy,
Williams Jacqueline P.,
O'Banion M. Kerry
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23288
Subject(s) - oligodendrocyte , biology , white matter , progenitor cell , central nervous system , population , progenitor , cancer research , neuroscience , pathology , stem cell , medicine , microbiology and biotechnology , myelin , magnetic resonance imaging , environmental health , radiology
Ionizing radiation (IR) is commonly used to treat central nervous system (CNS) cancers and metastases. While IR promotes remission, frequent side effects including impaired cognition and white matter loss occur following treatment. Fractionation is used to minimize these CNS late side effects, as it reduces IR effects in differentiated normal tissue, but not rapidly proliferating normal or tumor tissue. However, side effects occur even with the use of fractionated paradigms. Oligodendrocyte progenitor cells (OPCs) are a proliferative population within the CNS affected by radiation. We hypothesized that fractionated radiation would lead to OPC loss, which could contribute to the delayed white matter loss seen after radiation exposure. We found that fractionated IR induced a greater early loss of OPCs than an equivalent single dose exposure. Furthermore, OPC recovery was impaired following fractionated IR. Finally, reduced OPC differentiation and mature oligodendrocyte numbers occurred in single dose and fractionated IR paradigms. This work demonstrates that fractionation does not spare normal brain tissue and, importantly, highlights the sensitivity of OPCs to fractionated IR, suggesting that fractionated schedules may promote white matter dysfunction, a point that should be considered in radiotherapy.