Ultra-High-Dose-Rate FLASH Irradiation Limits Reactive Gliosis in the Brain.
Journal
Radiation research
ISSN: 1938-5404
Titre abrégé: Radiat Res
Pays: United States
ID NLM: 0401245
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
01
03
2020
accepted:
18
06
2020
pubmed:
28
8
2020
medline:
9
3
2021
entrez:
28
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32853387
pii: 442753
doi: 10.1667/RADE-20-00067.1
pmc: PMC7856066
mid: NIHMS1656709
doi:
Substances chimiques
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
636-645Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001416
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA244091
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA062203
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089575
Pays : United States
Informations de copyright
©2020 by Radiation Research Society. All rights of reproduction in any form reserved.
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