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

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.

authors

Montay-Gruel P,Acharya MM,Petersson K,Alikhani L,Yakkala C,Allen BD,Ollivier J,Petit B,Jorge PG,Syage AR,Nguyen TA,Baddour AAD,Lu C,Singh P,Moeckli R,Bochud F,Germond JF,Froidevaux P,Bailat C,Bourhis J,Vozenin MC

doi

10.1073/pnas.1901777116

subject

Has Abstract

pub_date

2019-05-28 00:00:00

pages

10943-10951

issue

22

eissn

0027-8424

issn

1091-6490

pii

1901777116

journal_volume

116

pub_type

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