Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain

Abstract

Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood–brain barrier dysfunctionality are considered among the main causative factors. Chronic neuroinflammation and altered immune reactions in the brain, which are inherent complications of brain irradiation, have also been directly implicated in the development of cognitive decline after radiation. This review aims to give a comprehensive overview on radiation-induced immune alterations and inflammatory reactions in the brain and summarizes how these processes can influence cognitive performance. The available data on the risk of low-dose radiation exposure in the development of cognitive impairment and the underlying mechanisms are also discussed.

Chronic radiation-induced brain changes after irradiation of endocranium

“…Circulus vitiosus is created, so DPS are most probably the consequence of chronic low-level neuroinflammation (17). Our study results match the current hypothesis (16,17).…”

“…Other studies showed the correlation between hydrocephalus and radiation-induced fibrosis, which disables resorption of cerebrospinal fluid (15). In most cases, hydrocephalus represents the consequence of surgical procedures which involve opening of the ventricular system of the brain (13)(14)(15)(16). In other study results, hydrocephalus appeared in 10% of the patients 10 years after the completion of radiation (15).…”

Role of Exosomes in Cancer-Related Cognitive Impairment

“…The use of radiation therapy in the treatment of a variety of CNS-related malignancies can affect brain structure and function, leading to cognitive deterioration [102]. Radiation used in cancer therapy can also activate the biogenesis and induce exosome secretion from cancer cells [103].…”

“…Although the precise mechanisms underlying CRCI remain to be established, several studies suggest there is a link between exosomes and CRCI. Exosome biogenesis, its cargo content, function, and activity may be influenced by cancer [97], cancer therapies [93,102], genetics [54,111], age [71], existing comorbidities [112,113], lifestyle [114,115], and environmental [116] factors. Differences in exosomal content (e.g., miRNAs and proteins) and release may exert protective or damaging effects that could alter the brain and CNS function, and cause declining cognitive health in cancer survivors.…”

Ionizing radiation modulates vascular endothelial growth factor expression through STAT3 signaling pathway in rat neonatal primary astrocyte cultures

“…The main pathological manifestation of RBI is cerebral angioedema, which mainly involves the abnormal proliferation of blood vessels in the brain (Lumniczky, Szatmári, & Sáfrány, ; Sona & Marian, ). Among them, vascular endothelial growth factor (VEGF) plays a key role (Andrews et al, ).…”