Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.

Details

Serval ID
serval:BIB_60FFC8628F81
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Montay-Gruel P., Acharya M.M., Petersson K., Alikhani L., Yakkala C., Allen B.D., Ollivier J., Petit B., Jorge P.G., Syage A.R., Nguyen T.A., Baddour AAD, Lu C., Singh P., Moeckli R., Bochud F., Germond J.F., Froidevaux P., Bailat C., Bourhis J., Vozenin M.C., Limoli C.L.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
28/05/2019
Peer-reviewed
Oui
Volume
116
Number
22
Pages
10943-10951
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s <sup>-1</sup> ). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy⋅s <sup>-1</sup> ) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.
Keywords
Animals, Brain/pathology, Brain/radiation effects, Cognitive Dysfunction/etiology, Cognitive Dysfunction/prevention & control, Female, Inflammation, Mice, Mice, Inbred C57BL, Neuroprotection/radiation effects, Radiation Dosage, Radiotherapy/adverse effects, Radiotherapy/methods, Reactive Oxygen Species/analysis, Reactive Oxygen Species/metabolism, cognitive dysfunction, neuroinflammation, neuronal morphology, reactive oxygen species, ultra-high dose-rate irradiation
Pubmed
Web of science
Open Access
Yes
Create date
25/05/2019 12:58
Last modification date
27/04/2020 5:20
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