Extracellular vesicles released after cranial radiation: An insight into an early mechanism of brain injury

Brain Res. 2022 May 1:1782:147840. doi: 10.1016/j.brainres.2022.147840. Epub 2022 Feb 17.

Abstract

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.

Keywords: Extracellular vesicles; Lipid peroxidation; Oxidative stress; Radiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain / metabolism
  • Brain Injuries* / etiology
  • Brain Injuries* / metabolism
  • Extracellular Vesicles* / metabolism
  • Mice
  • Neurons / metabolism
  • Proteins / metabolism

Substances

  • Proteins