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

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.