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

Authors :
Montay-Gruel, Pierre
Montay-Gruel, Pierre
Acharya, Munjal M
Petersson, Kristoffer
Alikhani, Leila
Yakkala, Chakradhar
Allen, Barrett D
Ollivier, Jonathan
Petit, Benoit
Jorge, Patrik Gonçalves
Syage, Amber R
Nguyen, Thuan A
Baddour, Al Anoud D
Lu, Celine
Singh, Paramvir
Moeckli, Raphael
Bochud, François
Germond, Jean-François
Froidevaux, Pascal
Bailat, Claude
Bourhis, Jean
Vozenin, Marie-Catherine
Limoli, Charles L
Montay-Gruel, Pierre
Montay-Gruel, Pierre
Acharya, Munjal M
Petersson, Kristoffer
Alikhani, Leila
Yakkala, Chakradhar
Allen, Barrett D
Ollivier, Jonathan
Petit, Benoit
Jorge, Patrik Gonçalves
Syage, Amber R
Nguyen, Thuan A
Baddour, Al Anoud D
Lu, Celine
Singh, Paramvir
Moeckli, Raphael
Bochud, François
Germond, Jean-François
Froidevaux, Pascal
Bailat, Claude
Bourhis, Jean
Vozenin, Marie-Catherine
Limoli, Charles L
Source :
Proceedings of the National Academy of Sciences of the United States of America; vol 116, iss 22, 10943-10951; 0027-8424
Publication Year :
2019

Abstract

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s-1). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy⋅s-1) 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.

Details

Database :
OAIster
Journal :
Proceedings of the National Academy of Sciences of the United States of America; vol 116, iss 22, 10943-10951; 0027-8424
Notes :
application/pdf, Proceedings of the National Academy of Sciences of the United States of America vol 116, iss 22, 10943-10951 0027-8424
Publication Type :
Electronic Resource
Accession number :
edsoai.on1367449028
Document Type :
Electronic Resource