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Original Research | Open Access

X-ray-based ultra-high dose rate FLASH radiotherapy mitigates acute radiation-induced hippocampal injury and inflammation

Renke Hea,b,c, Jiayu Liub, Bingxian Wanga,b, Hanbo Zhanga,b, Shengqiang Xiea,b, Yiyuan Zhangd, Xianhong Liue, Jianxin Wangf, Dai Wuf, Lehui Dud, Baolin Qud, Gang Chengb, Jianning Zhangb
PLA Medical School, Beijing 100853, China
Senior Department of Neurosurgery, the First Medical Center of PLA General Hospital, Beijing 100853, China
Beijing Institute of Basic Medical Sciences, Beijing 100853, China
Department of Radiation Oncology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Zhongjiu Flash Medical Technology Co., Ltd. Mianyang 621000, Sichuan, China
Institute of Applied Electronics, China Academy of Engineering Physics, Mianyang 621900, Sichuan, China
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Abstract

Background

To compare neural damage induced by ultra-high dose rate FLASH radiotherapy (FLASH-RT) with that induced by conventional dose rate radiotherapy (CONV-RT) in healthy mice.

Methods

Eighty adult male C57BL/6J mice were divided into five groups: Sham, CONV-RT10Gy, CONV-RT20Gy, FLASH-RT10Gy, and FLASH-RT20Gy. Three days post-irradiation, morphological changes in neurons within the dentate gyrus (DG), CA1, and CA3 were observed using hematoxylin and eosin and Nissl staining. The malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), catalase (CAT), and hydroxyl radical (OH−) levels were measured using assay kits. Quantitative reverse transcription PCR was used to assess interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α mRNA expression levels in hippocampus. Immunofluorescence was employed to observe microglial activation in the DG.

Results

Compared with Sham, CONV-RT10Gy and CONV-RT20Gy exhibited disorganized neuronal arrangements and blurred nucleoli in the DG; the number of Nissl body was reduced, but FLASH-RT10Gy and FLASH-RT20Gy alleviated these abnormalities. Moreover, FLASH-RT20Gy mitigated the upregulation of MDA and downregulation of GSH, GSH-PX, SOD, CAT, and OH− levels in the hippocampus of mice subjected to CONV-RT20Gy. Additionally, FLASH-RT20Gy attenuated the upregulation of IL-1β, IL-6, iNOS, and TNF-α mRNA levels in hippocampus of mice subjected to CONV-RT20Gy and diminished microglial activation in the DG.

Conclusion

FLASH-RT mitigate the structural and functional disruptions in hippocampal neurons induced by CONV-RT and alleviate oxidative stress and inflammation in hippocampal tissue by reducing microglial activation.

Keywords

FLASH radiotherapyRadiation-induced brain injuryUltra-high dose rateFLASH effectOxidative stressCONV radiotherapy

Electronic Supplementary Material

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Journal of Neurorestoratology
Volume 13 Issue 2,
April 2025
DOI: 10.1016/j.jnrt.2025.100186
Cite this article:
He R, Liu J, Wang B, et al. X-ray-based ultra-high dose rate FLASH radiotherapy mitigates acute radiation-induced hippocampal injury and inflammation. Journal of Neurorestoratology, 2025, 13(2). https://doi.org/10.1016/j.jnrt.2025.100186

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Received: 16 September 2024
Revised: 18 November 2024
Accepted: 17 December 2024
Published: 01 April 2025
© 2025

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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