Radiation-Induced Neuroinflammation and Radiation Somnolence Syndrome

Abstract

Cranial irradiation remains a standard treatment for malignant and benign brain diseases. Although this procedure helps to lengthen the life expectancy of the patient, the appearance of adverse effects related to radiation-induced injury is inevitable. Radiation somnolence syndrome (RSS) has been described as a delayed effect observed mainly after whole-brain radiotherapy in children. The RSS was first linked to demyelination, but more recently it has been proposed that the inflammatory response plays a primary role in the aforementioned syndrome. To evaluate the feasibility of this hypothesis, we explored previous work about RSS and reviewed published research that included measurements of the inflammatory response in models of brain exposure to ionizing radiation. Pro-inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, interleukin-6 and interleukin-18 as well as other inflammatory markers such as cyclooxygenase-2, prostaglandin E₂, glial fibrillary acid protein, intercellular adhesion molecule-1 and nuclear factor-κB appear to be involved in the brain's response to radiation. However, certain publications have described the somnogenic effects of these cytokines and inflammatory markers. Although the radiation response is a complex phenomenon that involves several molecular and cellular processes, we propose that inflammation may be closely related to the adverse effects of brain irradiation and therefore to the etiology of RSS.

Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders

“…It has been reported that deficient neurogenesis following cranial irradiation of rats is not caused by irradiation itself, but rather by the neuroinflammatory response resulting from radiation-induced tissue damages [69]. Indeed, in rodents, irradiation of the head results in reactive gliosis by both astrocytes and microglia [70,71]. In line with this, a marked increase in the activation and proliferation of microglial cells was observed in the hippocampus after a single dose of 10 Gy irradiation and was sustained over several months [65,72,73].…”

A new paradigm in treatment of brain metastases

“…Some patients experience mild otitis or transient Eustachian tube dysfunction. A delayed period of fatigue or somnolence following WBRT has been described, particularly in children but also in adults, and may be related to temporary demyelination or inflammatory response [64] [65]. The potential late toxicities of whole brain radiation therapy include an increased risk of cataracts, though the long average latency period to development of radiation-induced cataracts [66] renders this of little importance to the vast majority of patients with brain metastases.…”

Cytokines: shifting the balance between glioma cells and tumor microenvironment after irradiation

“…Irradiated microglial cells produce a dose-dependent increase of IL-1β, IL-6, IL-18, TnF-α, and IFn-γ-inducible protein-10, which are involved in the process of IR-induced astrocyte gliosis (hwang et al 2006). Pro-inflammatory cytokines such as IL-1β, TnF-α, IL-6, and IL-18 participate in IR somnolence syndrome (Ballesteros-Zebadúa et al 2012). Cytokines induce proteolysis and lipolysis, which are also involved in the cause of malnutrition and cachexia in cancer patients, including IL-1, IL-6, IFn-γ, TnF-α, and brain-derived neurotrophic factor (BDnF) (Katsuramaki et al 1998;Plata-salamán 2000).…”