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Resumen

Cranial radiation is important for treating both primary brain tumors and brain metastases. A potential delayed side effect of cranial radiation is neurocognitive function decline. Early detection of CNS injury might prevent further neuronal damage. Extracellular vesicles (EVs) have emerged as a potential diagnostic tool because of their unique membranous characteristics and cargos. We investigated whether EVs can be an early indicator of CNS injury by giving C57BJ/6 mice 10 Gy cranial IR. EVs were isolated from sera to quantify: 1) number of EVs using nanoparticle tracking analysis (NTA); 2) Glial fibrillary acidic protein (GFAP), an astrocyte marker; and 3) protein-bound 4-hydroxy-2-nonenal (HNE) adducts, an oxidative damage marker. Brain tissues were prepared for immunohistochemistry staining and protein immunoblotting. The results demonstrate: 1) increased GFAP levels (p < 0.05) in EVs, but not brain tissue, in the IR group; and 2) increased HNE-bound protein adduction levels (p < 0.05). The results support using EVs as an early indicator of cancer therapy-induced neuronal injury.

Idioma originalEnglish
Número de artículo147840
PublicaciónBrain Research
Volumen1782
DOI
EstadoPublished - may 1 2022

Nota bibliográfica

Publisher Copyright:
© 2022 The Authors

Financiación

This work was supported by the National Institutes of Health (5R01CA217934-04), National Institute of Environmental Health Sciences (T32ES07266), the National Cancer Institute Cancer Center Support Grant (P30 CA177558), the National Institue of General Medical Sciences (P20 P20 GM121327), and the University of Kentucky Center for Clinical and Translational Science (NIH-UL1TR001998). The authors would like to acknowledge the Biospecimen Procurement and Translational Pathology Shared Resource Facility (Dana Napier and Dr. Therese Bocklage), the Redox Metabolism Shared Resource Facility (Michael Alstott), and the Biostatistics and Bioinformatics Shared Resource Facility at the Markey Cancer Center. This work was supported by the National Institutes of Health (5R01CA217934-04), National Institute of Environmental Health Sciences (T32ES07266), the National Cancer Institute Cancer Center Support Grant (P30 CA177558), the National Institue of General Medical Sciences (P20 P20 GM121327), and the University of Kentucky Center for Clinical and Translational Science (NIH-UL1TR001998).

FinanciadoresNúmero del financiador
National Institutes of Health (NIH)
The Markey Biostatistics and Bioinformatics Shared Resource Facility
Markey Cancer Center Redox and Metabolism Shared Resource Facility
University of Kentucky, Center for Clinical and Translational ScienceNIH-UL1TR001998
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical SciencesP20GM121327
National Childhood Cancer Registry – National Cancer InstituteR01CA217934, P30CA177558
National Institutes of Health/National Institute of Environmental Health SciencesT32ES007266
National Center for Advancing Translational Sciences (NCATS)UL1TR001998

    ODS de las Naciones Unidas

    Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

    1. Good health and well being
      Good health and well being

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • Clinical Neurology
    • Developmental Biology

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