Radiation-induced neuropathological changes in the oligodendrocyte lineage with relevant clinical manifestations and therapeutic strategies

Abstract

Purpose

With technological advancements in radiation therapy for tumors of the central nervous system (CNS), high doses of ionizing radiation can be delivered to the tumors with improved accuracy. Despite the reduction of ionizing radiation-induced toxicity to surrounding tissues of the CNS, a wide array of side effects still occurs, particularly late-delayed changes. These alterations, such as white matter damages and neurocognitive impairments, are often debilitative and untreatable, significantly affecting the quality of life of these patients, especially children. Oligodendrocytes, a major class of glial cells, have been identified to be one of the targets of radiation toxicity and are recognized be involved in late-delayed radiation-induced neuropathological changes. These cells are responsible for forming the myelin sheaths that surround and insulate axons within the CNS. Here, the effects of ionizing radiation on the oligodendrocyte lineage as well as the common clinical manifestations resulting from radiation-induced damage to oligodendrocytes will be discussed. Potential prophylactic and therapeutic strategies against radiation-induced oligodendrocyte damage will also be considered.

Conclusion

Oligodendrocytes and oligodendrocyte progenitor cells (OPCs) are radiosensitive cells of the CNS. Here, general responses of these cells to radiation exposure have been outlined. However, several findings have not been consistent across various studies. For instance, cognitive decline in irradiated animals was observed to be accompanied by obvious demyelination or white matter changes in several studies but not in others. Hence, further studies have to be conducted to elucidate the level of contribution of the oligodendrocyte lineage to the development of late-delayed effects of radiation exposure, as well as to classify the dose and brain region-specific responses of the oligodendrocyte lineage to radiation. Several potential therapeutic approaches against late-delayed changes have been discussed, such as the transplantation of OPCs into irradiated regions and implementation of exercise. Many of these approaches show promising results. Further elucidation of the mechanisms involved in radiation-induced death of oligodendrocytes and OPCs would certainly aid in the development of novel protective and therapeutic strategies against the late-delayed effects of radiation.

Keywords:

• Oligodendrocytes
• oligodendrocyte progenitor cells
• radiation
• demyelination
• white matter necrosis
• cognitive impairment

Acknowledgements

We would like to thank the National Research Foundation of Singapore for their support to the Singapore Nuclear Research and Safety Initiative (TFR), thereby making this review possible.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This review is funded by the National Research Foundation of Singapore.

Notes on contributors

Rui Xue Lee

Rui Xue Lee works as a Research Assistant with the Singapore Nuclear Research and Safety Initiative, in the Department of Radiation Physiology. She received her Bachelor’s of Science with First Class Honors from the National University of Singapore (NUS) in 2020 and is currently pursuing her graduate studies with NUS Yong Loo Lin School of Medicine. She is a recipient of the President’s Graduate Fellowship and has also won numerous scholarships and awards throughout her academic journey.

Feng Ru Tang

Feng Ru Tang is a Senior Research Scientist at the Singapore Nuclear Research and Safety Initiative in National University of Singapore. His research focus includes (but not limited to) the investigation of the brain effect of pre- and post-natal radiation exposure and the relevant molecular mechanisms, and the development of biomarkers for early detection of radiation exposure and related brain damage.