Radiation therapy is a critical tool for the treatment of brain tumors, however, exposure to high doses of ionizing radiation (IR) causes numerous central nervous system side-effects, including declines in cognitive function, memory, and attention. Brain injury from IR is characterized by numerus inflammatory effects, including white matter damage from the loss of myelin-producing oligodendrocyte cells. While neuro-oncology outcomes are often concerned with survival, strategies to understand and ameliorate radiation-induced damage after IR treatment are needed to preserve and improve patient quality of life. Our lab is interested in studying the differential effects of radiation on oligodendrocyte cells, as they comprise the majority of white matter in the brain, and methods to halt radiation-induced damage. We have established a mass spectrometry-based metabolomics method to study radiation-injury in cells, tissue, and biofluids, and are applying this technique to study radiation effects on the MO3.13 oligodendrocyte cell line. We are currently investigating the ability of dimethyl fumarate (DMF), an established neuroprotective agent, to amend damage and demyelination to oligodendrocyte cells versus glioma cells, after X-irradiation. Using metabolomics, we noted that oligodendrocyte cells upregulated tricarboxylic acid (TCA) cycle intermediates in response to DMF treatment, with sustained levels after radiation. In addition, measured levels of glutathione were elevated, and markers for generalized oxidative stress were comparably lower with DMF pretreatment. Ultimately, this information could be used to prevent radiation-induced demyelination, promoting patient quality of life.

 

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