Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?

Abstract

Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography–mass spectrometry in a rat model

“…They are linked to the development of hypertension and related disease (Laiakis et al, ). Moreover, a growing number of multiaspect information points to the direct involvement of neuroinflammation in the pathogenesis of various radiation‐induced brain injuries, including necrosis and cognitive impairments (Lumniczky et al, ; Piskunov et al, ). Thus, the accumulated AA in brain tissue (Figure S3) suggests that the inflammation response is activated in nervous system damage at an acute stage after radiation exposure.…”

“…The acute symptoms are mostly transient, reversible and respond to corticosteroid treatment. In contrast, the late delayed radiation‐induced changes are progressive and irreversible (Piskunov, Nikitin, & Potapov, ). Therefore, investigating the early metabolic characterization of brain tissues following irradiation may present clues to the mechanism of radiation‐induced brain injury and modify the therapeutic strategy.…”

Biomarkers of Brain Damage Induced by Radiotherapy

“…Therefore, the technique for measurement of MGMT methylation process could determine radiosensitivity and radiation-induced necrosis development. 14…”

“…Antiaquaporin-4 antibodies in blood serum by molecular diagnosis indicated the demyelination of brain cells in patients with tumor after cranial RT. 14 Neuron-specific enolase, a neuroendocrine processing glycolytic enzyme, and S100 calcium-binding protein B, a nervous system specific cytoplasmic protein generated by astrocytes when the BBB was ruptured, were regarded as the prospective markers for screening endothelial and neuronal injury. As particular markers, increased neuron-specific enolase denoted brain metastases and predicted shorter survival, 82 , 83 an elevated level of S100 calcium-binding protein B in the circulating blood indicated BBB damage, 95 brain metastasis, 96 and predicted melanoma brain metastases.…”

“… 85 Studies also showed that neuron-specific enzyme ubiquitin C-terminal hydrolase, the fragment of proteolytic cleavage of the N-methyl- d -aspartate receptor or N-methyl- d -aspartate receptor antibodies, endothelial monocyte-activating polypeptide-II cytokine, and nitrotyrosine could correlate with brain injury following RT. 14 These molecules could be regarded as potential biomarkers and a high level of these molecules in blood serum implied the severity of radiation-induced brain damage.…”