Translator Disclaimer
16 July 2021 Spatially Fractionated X-Ray Microbeams Elicit a More Sustained Immune and Inflammatory Response in the Brainstem than Homogenous Irradiation
Lloyd M. L. Smyth, Jeffrey C. Crosbie, Clare Sloggett, Peter A. W. Rogers, Jacqueline F. Donoghue
Author Affiliations +
Abstract

Synchrotron microbeam radiation therapy (MRT) is a preclinical irradiation technique which could be used to treat intracranial malignancies. The goal of this work was to discern differences in gene expression and the predicted regulation of molecular pathways in the brainstem after MRT versus synchrotron broad-beam radiation therapy (SBBR). Healthy C57BL/6 mice received whole-head irradiation with median acute toxic doses of MRT (241 Gy peak dose) or SBBR (13 Gy). Brains were harvested 4 and 48 h postirradiation and RNA was extracted from the brainstem. RNA-sequencing was performed to identify differentially expressed genes (false discovery rate < 0.01) relative to nonirradiated controls and significantly regulated molecular pathways and biological functions were identified (Benjamini-Hochberg corrected P < 0.05). Differentially expressed genes and regulated pathways largely reflected a pro-inflammatory response 4 h after both MRT and SBBR which was sustained at 48 h postirradiation for MRT. Pathways relating to radiation-induced viral mimicry, including HMGB1, NF-κB and interferon signaling cascades, were predicted to be uniquely activated by MRT. Local microglia, as well as circulating leukocytes, including T cells, were predicted to be activated by MRT. Our findings affirm that the transcriptomic signature of MRT is distinct from broad-beam radiotherapy, with a sustained inflammatory and immune response up to 48 h postirradiation.

©2021 by Radiation Research Society. All rights of reproduction in any form reserved.
Lloyd M. L. Smyth, Jeffrey C. Crosbie, Clare Sloggett, Peter A. W. Rogers, and Jacqueline F. Donoghue "Spatially Fractionated X-Ray Microbeams Elicit a More Sustained Immune and Inflammatory Response in the Brainstem than Homogenous Irradiation," Radiation Research 196(4), 355-365, (16 July 2021). https://doi.org/10.1667/RADE-20-00082.1
Received: 27 March 2020; Accepted: 22 June 2021; Published: 16 July 2021
JOURNAL ARTICLE
11 PAGES


SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top