Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_932C4B78C34E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation.
Journal
Cancers
Author(s)
Alaghband Y., Cheeks S.N., Allen B.D., Montay-Gruel P., Doan N.L., Petit B., Jorge P.G., Giedzinski E., Acharya M.M., Vozenin M.C., Limoli C.L.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
24/06/2020
Peer-reviewed
Oui
Volume
12
Number
6
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients' quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective "FLASH effect" was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin <sup>+</sup> ) and mature (NeuN <sup>+</sup> ) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors.
Keywords
FLASH radiotherapy, cognitive dysfunction, juvenile mice, medulloblastoma, memory consolidation, neurogenesis, pediatric brain cancer, updating task
Pubmed
Open Access
Yes
Create date
03/07/2020 16:25
Last modification date
15/01/2021 7:10
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