A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints.

Details

Serval ID
serval:BIB_CB544F6123D0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints.
Journal
Radiotherapy and oncology
Author(s)
Drayson OGG, Melemenidis S., Katila N., Viswanathan V., Kramár E.A., Zhang R., Kim R., Ru N., Petit B., Dutt S., Manjappa R., Ramish Ashraf M., Lau B., Soto L., Skinner L., Yu A.S., Surucu M., Maxim P.G., Zebadua-Ballasteros P., Wood M.A., Gruel P.M., Baulch J.E., Vozenin M.C., Loo B.W., Limoli C.L.
ISSN
1879-0887 (Electronic)
ISSN-L
0167-8140
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions.
We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints.
FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH.
In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.
Keywords
Electrophysiology, FLASH, Intercomparison, Neurobehavior, Neurogenesis, Neuroinflammation, Radiotherapy
Pubmed
Open Access
Yes
Create date
20/09/2024 16:01
Last modification date
21/09/2024 7:10
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