文章基本信息

标题：Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species
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作者：Pierre Montay-Gruel ; Pierre Montay-Gruel ; Munjal M. Acharya 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：22
页码：10943-10951
DOI：10.1073/pnas.1901777116
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：ultra-high dose-rate irradiation ; cognitive dysfunction ; neuronal morphology ; neuroinflammation ; reactive oxygen species