Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species
(2019) In Proceedings of the National Academy of Sciences of the United States of America 166(22). p.10943-10951- 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... (More)
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.
(Less)
- author
- publishing date
- 2019-05-28
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cognitive dysfunction, Neuroinflammation, Neuronal morphology, Reactive oxygen species, Ultra-high dose-rate irradiation
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 166
- issue
- 22
- pages
- 9 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:31097580
- scopus:85066269490
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1901777116
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2019 National Academy of Sciences. All rights reserved.
- id
- c7e8224b-43aa-4cfa-8ffd-d984f2b2c7ff
- date added to LUP
- 2021-11-03 18:17:53
- date last changed
- 2024-04-20 15:45:00
@article{c7e8224b-43aa-4cfa-8ffd-d984f2b2c7ff, abstract = {{<p>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.</p>}}, author = {{Montay-Gruel, Pierre and Acharya, Munjal M. and Petersson, Kristoffer and Alikhani, Leila and Yakkala, Chakradhar and Allen, Barrett D. and Ollivier, Jonathan and Petit, Benoit and Jorge, Patrik Gonçalves and Syage, Amber R. and Nguyen, Thuan A. and Baddour, Al Anoud D. and Lu, Celine and Singh, Paramvir and Moeckli, Raphael and Bochud, François and Germond, Jean François and Froidevaux, Pascal and Bailat, Claude and Bourhis, Jean and Vozenin, Marie Catherine and Limoli, Charles L.}}, issn = {{0027-8424}}, keywords = {{Cognitive dysfunction; Neuroinflammation; Neuronal morphology; Reactive oxygen species; Ultra-high dose-rate irradiation}}, language = {{eng}}, month = {{05}}, number = {{22}}, pages = {{10943--10951}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences of the United States of America}}, title = {{Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species}}, url = {{http://dx.doi.org/10.1073/pnas.1901777116}}, doi = {{10.1073/pnas.1901777116}}, volume = {{166}}, year = {{2019}}, }