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

Détails

ID Serval
serval:BIB_60FFC8628F81
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(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
Statut éditorial
Publié
Date de publication
28/05/2019
Peer-reviewed
Oui
Volume
116
Numéro
22
Pages
10943-10951
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.
Mots-clé
cognitive dysfunction, neuroinflammation, neuronal morphology, reactive oxygen species, ultra-high dose-rate irradiation
Pubmed
Web of science
Création de la notice
25/05/2019 12:58
Dernière modification de la notice
20/08/2019 14:18
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