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Radiation-induced redox alteration in the mouse brain
Mizuki Nakamura1, Toshihide Yamasaki2, Megumi Ueno3
1Quantitative RedOx Sensing Group, Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan; Graduate School of Medical and Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-88670, Japan.
Magnetic resonance redox imaging revealed distinct brain redox responses to X-ray and carbon-ion beam irradiation in mice. Carbon-ion beam exposure induced more acute and severe oxidative stress compared to X-ray radiation.
Area of Science:
- Neuroscience
- Radiology
- Biophysics
Background:
- Radiation therapy, including X-ray and carbon-ion beam (C-beam) irradiation, can induce oxidative stress in the brain.
- Understanding the temporal dynamics of redox status post-irradiation is crucial for assessing neurotoxicity and optimizing treatment strategies.
- Magnetic Resonance Redox Imaging (MRRI) offers a non-invasive method to probe brain redox environments.
Purpose of the Study:
- To investigate and compare the time-dependent changes in brain redox status following X-ray and C-beam irradiation using MRRI.
- To elucidate the relationship between radiation-induced oxidative stress and the observed changes in brain redox dynamics.
- To differentiate the specific redox responses elicited by X-ray versus C-beam irradiation.
Main Methods:
- Mice were subjected to 8-Gy X-ray or C-beam irradiation to the head under anesthesia.
- Magnetic Resonance Redox Imaging (MRRI) was performed using a 7-T scanner with blood-brain-barrier-permeable nitroxyl contrast agents (MCP or TEMPOL).
- Measurements were taken at multiple time points (5-10 hours, 1, 2, 4, and 8 days post-irradiation) to assess T1-weighted MR signal decay rates, reflecting redox status.
Main Results:
- Both X-ray and C-beam irradiation initially caused a decrease in apparent nitroxyl decay rates, attributed to reduced blood flow.
- Following this initial decrease, decay rates gradually increased after X-ray irradiation and rapidly increased 1 day after C-beam irradiation.
- Distinct temporal patterns in redox response were observed between X-ray and C-beam irradiation, with C-beam effects being more acute and pronounced.
- The observed increases in decay rates suggest increased reactive oxygen species (ROS) generation and oxidative atmosphere in the brain tissue.
Conclusions:
- X-ray and C-beam irradiation induce differential redox responses in the mouse brain, likely due to time-varying oxidative stress.
- Carbon-ion beam irradiation elicits a more rapid and intense oxidative stress response compared to X-ray irradiation.
- MRRI is a valuable tool for characterizing the spatio-temporal dynamics of radiation-induced oxidative stress in the brain.