Ultra-High-Dose-Rate FLASH Irradiation Limits Reactive Gliosis in the Brain.

Details

Serval ID
serval:BIB_82F091805B85
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ultra-High-Dose-Rate FLASH Irradiation Limits Reactive Gliosis in the Brain.
Journal
Radiation research
Author(s)
Montay-Gruel P., Markarian M., Allen B.D., Baddour J.D., Giedzinski E., Jorge P.G., Petit B., Bailat C., Vozenin M.C., Limoli C., Acharya M.M.
ISSN
1938-5404 (Electronic)
ISSN-L
0033-7587
Publication state
Published
Issued date
01/12/2020
Peer-reviewed
Oui
Volume
194
Number
6
Pages
636-645
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Encephalic radiation therapy delivered at a conventional dose rate (CONV, 0.1-2.0 Gy/min) elicits a variety of temporally distinct damage signatures that invariably involve persistent indications of neuroinflammation. Past work has shown an involvement of both the innate and adaptive immune systems in modulating the central nervous system (CNS) radiation injury response, where elevations in astrogliosis, microgliosis and cytokine signaling define a complex pattern of normal tissue toxicities that never completely resolve. These side effects constitute a major limitation in the management of CNS malignancies in both adult and pediatric patients. The advent of a novel ultra-high dose-rate irradiation modality termed FLASH radiotherapy (FLASH-RT, instantaneous dose rates ≥106 Gy/s; 10 Gy delivered in 1-10 pulses of 1.8 µs) has been reported to minimize a range of normal tissue toxicities typically concurrent with CONV exposures, an effect that has been coined the "FLASH effect." Since the FLASH effect has now been found to significantly limit persistent inflammatory signatures in the brain, we sought to further elucidate whether changes in astrogliosis might account for the differential dose-rate response of the irradiated brain. Here we report that markers selected for activated astrogliosis and immune signaling in the brain (glial fibrillary acidic protein, GFAP; toll-like receptor 4, TLR4) are expressed at reduced levels after FLASH irradiation compared to CONV-irradiated animals. Interestingly, while FLASH-RT did not induce astrogliosis and TLR4, the expression level of complement C1q and C3 were found to be elevated in both FLASH and CONV irradiation modalities compared to the control. Although functional outcomes in the CNS remain to be cross-validated in response to the specific changes in protein expression reported, the data provide compelling evidence that distinguishes the dose-rate response of normal tissue injury in the irradiated brain.
Pubmed
Web of science
Create date
09/09/2020 11:51
Last modification date
17/02/2021 7:27
Usage data